A Randomized Trial of Endometrial Scratching before In Vitro Fertilization
Open accessAbstract
BACKGROUND: Endometrial scratching (with the use of a pipelle biopsy) is a technique proposed to facilitate embryo implantation and increase the probability of pregnancy in women undergoing in vitro fertilization (IVF). METHODS: We conducted a pragmatic, multicenter, open-label, randomized, controlled trial. Eligible women were undergoing IVF (fresh-embryo or frozen-embryo transfer), with no recent exposure to disruptive intrauterine instrumentation (e.g., hysteroscopy). Participants were randomly assigned in a 1:1 ratio to either endometrial scratching (by pipelle biopsy between day 3 of the cycle preceding the embryo-transfer cycle and day 3 of the embryo-transfer cycle) or no intervention. The primary outcome was live birth. RESULTS: A total of 1364 women underwent randomization. The frequency of live birth was 180 of 690 women (26.1%) in the endometrial-scratch group and 176 of 674 women (26.1%) in the control group (adjusted odds ratio, 1.00; 95% confidence interval, 0.78 to 1.27). There were no significant between-group differences in the rates of ongoing pregnancy, clinical pregnancy, multiple pregnancy, ectopic pregnancy, or miscarriage. The median score for pain from endometrial scratching (on a scale of 0 to 10, with higher scores indicating worse pain) was 3.5 (interquartile range, 1.9 to 6.0). CONCLUSIONS: Endometrial scratching did not result in a higher rate of live birth than no intervention among women undergoing IVF. (Funded by the University of Auckland and others; PIP Australian New Zealand Clinical Trials Registry number, ACTRN12614000626662 .).
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RCTs and meta-analyses in the IVF/ICSI context have failed to show a reduction in miscarriage rates with endometrial scratch/injury.
“although to date RCTs and meta-analyses in this patient group have failed to show a reduction in miscarriage rates.205,206”
From Recurrent MiscarriageGreen‐top Guideline No. 17 (2023) · cites this paper as [206]
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Self-citationLarge randomized controlled trials in infertility
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Self-citationEndometrial scratch injury with office hysteroscopy before IVF/ICSI: A randomised controlled trial
Berntsen, S., Hare, K. J., Løssl, K., Bogstad, J. W., Palmø, J., Prætorius, L., Zedeler, A., & Pinborg, A. B. (2020) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2020.06.034 · Cited by 19 · see citing works
A review of factors influencing the implantation of euploid blastocysts after in vitro fertilization
Reshef, E. A., Robles, A., Hynes, J. S., Turocy, J. M., & Forman, E. J. (2022) · F&S Reviews · doi:10.1016/j.xfnr.2022.03.001 · Cited by 23 · see citing works
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Farquhar, C. M. (2019) · Fertility and Sterility · doi:10.1016/j.fertnstert.2019.04.010 · Cited by 18 · see citing works
Self-citationEndometriosis and In Vitro Fertilization
Latif, S., Khanjani, S., & Sarıdoğan, E. (2024) · Medicina · doi:10.3390/medicina60081358 · Cited by 19 · see citing works
Galiano, V., Orvieto, R., Machtinger, R., Nahum, R., Garzia, E., Sulpizio, P., Marconi, A. M., & Seidman, D. S. (2021) · Reproductive Sciences · doi:10.1007/s43032-021-00601-7 · Cited by 17 · see citing works
van Hoogenhuijze, N. E., van EEKELEN, R., Mol, F., Schipper, I. B., Groenewoud, E. R., Traas, M. A. F., Janssen, C. A. H., Teklenburg, G., de Bruin, J. P., van Oppenraaij, R. H. F., et al. (2021) · Human Reproduction · doi:10.1093/humrep/deab261 · Cited by 17 · see citing works
Vitale, S. G., Angioni, S. L., Parry, J. P., Sardo, A. D. S., Haimovich, S., Carugno, J. A., Pacheco, L. A., Pérez‐Medina, T., Moawad, N. S., FRANCISCIS, P. D., et al. (2023) · Gynecologic and Obstetric Investigation · doi:10.1159/000534794 · Cited by 17 · see citing works
Izquierdo, A., Bitaine, L. D. L. F., Spies, K., Lora, D., & Galindo, A. (2020) · Reproductive Sciences · doi:10.1007/s43032-020-00204-8 · Cited by 16 · see citing works
IVF, from the past to the future: the inheritance of the Capri Workshop Group
The Annual Capri Workshop Group, Albertini, D. F., Crosignani, P., Dumoulin, J. C. M., Evers, J. L. H., Léridon, H., Mastenbroek, S., Painter, R. C., Pinborg, A., Somigliana, E., et al. (2020) · Human Reproduction Open · doi:10.1093/hropen/hoaa040 · Cited by 18 · see citing works
Ghasemi, M., Aleyasin, A., Fatemi, H. M., Ghaemdoust, F., & Shahrakipour, M. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.778988 · Cited by 16 · see citing works
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Vomstein, K., Egerup, P., Kolte, A. M., Behrendt-Møller, I., Boje, A. D., Bertelsen, M.-L. M. F., Eiken, C. S., Reiersen, M. R., Tóth, B., Freiesleben, N. L. C., et al. (2023) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2023.03.018 · Cited by 16 · see citing works
Immune Cell Functionality during Decidualization and Potential Clinical Application
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Adjuvants in IVF—evidence for what works and what does not work
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Endometrial preparation for third-party parenting and cryopreserved embryo transfer
Smith, M. B., & Paulson, R. J. (2019) · Fertility and Sterility · doi:10.1016/j.fertnstert.2019.02.010 · Cited by 16 · see citing works
A Randomized Trial of Endometrial Scratching before In Vitro Fertilization
Odendaal, J., & Quenby, S. M. (2019) · New England Journal of Medicine · doi:10.1056/nejmc1902642 · Cited by 16 · see citing works
Coordination and planning of clinical research on a national and global level
Devall, A., Out, H. J., Mol, B. W., Duffy, J. M., Collura, B. L., & Dyer, S. (2020) · Fertility and Sterility · doi:10.1016/j.fertnstert.2020.04.032 · Cited by 15 · see citing works
Iakovidou, M. C., Kolibianakis, E. M., Zepiridis, L. I., & Venetis, C. A. (2023) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-023-01141-2 · Cited by 15 · see citing works
The impact of endometrial injury on reproductive outcomes: results of an updated meta‐analysis
Nahshon, C., Sagi‐Dain, L., & Dirnfeld, M. (2020) · Reproductive Medicine and Biology · doi:10.1002/rmb2.12348 · Cited by 15 · see citing works
Endometrial injury for pregnancy following sexual intercourse or intrauterine insemination
Bui, B. N., Lensen, S. F., Gibreel, A., Martins, W. P., Torrance, H. L., & Broekmans, F. J. (2022) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011424.pub4 · Cited by 14 · see citing works
Self-citationTang, Z., Hong, M., He, F., Huang, D., Dai, Z., Xuan, H.-H., Zhang, H., & Zhu, W. (2020) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.14193 · Cited by 13 · see citing works
Endometrial scratching: is it all over?
Palomba, S., & Macklon, N. (2022) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2022.03.018 · Cited by 13 · see citing works
Tumanyan, A., Gemilyan, M., & Hambartsoumian, E. (2019) · Gynecological Endocrinology · doi:10.1080/09513590.2019.1632085 · Cited by 13 · see citing works
Tu, Y., Chou, C., Yang, P.-K., Shun, C., Wen, W.-F., Tsao, P., Chen, S., & Yang, J. (2021) · Molecular Human Reproduction · doi:10.1093/molehr/gaab055 · Cited by 13 · see citing works
Metwally, M., Chatters, R., White, D. A., Hall, J., & Walters, S. J. (2021) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2021.11.021 · Cited by 13 · see citing works
Rodriguez‐Wallberg, K. A., Kieler, H., Foukakis, T., Li, J., Gissler, M., Öberg, A. S., Bergh, J. C. S., & Lundberg, F. E. (2023) · EClinicalMedicine · doi:10.1016/j.eclinm.2023.102335 · Cited by 12 · see citing works
Enhancing uterine receptivity for embryo implantation through controlled collagenase intervention
Zehorai, E., Lev, T. G., Shimshoni, E., Hadas, R., Adir, I., Golani, O., Molodij, G., Eitan, R., Kadler, K. E., Kollet, Ó., et al. (2024) · Life Science Alliance · doi:10.26508/lsa.202402656 · Cited by 12 · see citing works
Glanville, E. J., Wilkinson, J., Sadler, L. C., Wong, T. Y., Acharya, S., Aziz, N., Clarke, F. R., Das, S., Dawson, J., Hammond, B., et al. (2021) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2021.10.008 · Cited by 12 · see citing works
Self-citationMetwally, M., Chatters, R., Pye, C., Dimairo, M., White, D., Walters, S., Cohen, J., Young, T., Cheong, Y. C., Laird, S., et al. (2022) · Health Technology Assessment · doi:10.3310/jnzt9406 · Cited by 13 · see citing works
Endometrial scratching for infertility: The never-ending story
Vitagliano, A., Vitale, S. G., Cianci, A., Ferrero, S., Barra, F., Andrisani, A., & Ambrosini, G. (2020) · Journal of Gynecology Obstetrics and Human Reproduction · doi:10.1016/j.jogoh.2020.101743 · Cited by 12 · see citing works
Metwally, M., Chatters, R., Pye, C., Dimairo, M., White, D., Walters, S., Cohen, J., Young, T., Cheong, Y., Laird, S., et al. (2022) · White Rose Research Online (University of Leeds, The University of Sheffield, University of York) · Cited by 11 · see citing works
Palomba, S., Vitagliano, A., Marci, R., & Caserta, D. (2022) · Reproductive Sciences · doi:10.1007/s43032-022-01125-4 · Cited by 11 · see citing works
Li, N., Zhang, Y., Li, R., Chen, Y.-L., Huang, L., Tan, Z., Ban, X., Zhou, L., Xu, C.-L., Qiu, Y., et al. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1369317 · Cited by 9 · see citing works
Endometrial Receptivity Testing and Therapy in Assisted Reproductive Treatment
Polański, Ł., & Baumgarten, M. N. (2021) · Seminars in Reproductive Medicine · doi:10.1055/s-0041-1730421 · Cited by 9 · see citing works
Wang, C., Guan, D., Li, R., Bing, Z., Yang, Y., & Yang, K. (2021) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2021.103429 · Cited by 9 · see citing works
Endometrial injury for pregnancy following sexual intercourse or intrauterine insemination
Bui, B. N., Lensen, S. F., Gibreel, A., Martins, W. P., Torrance, H. L., & Broekmans, F. J. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011424.pub3 · Cited by 10 · see citing works
Self-citationTargeted Endometrial Scratching: An Example of Endometrial Diagnosis Usage in Reproductive Medicine
Rahmati, M., & Lédée, N. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.589677 · Cited by 9 · see citing works
Tesařík, J., & Mendoza‐Tesarik, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810357 · Cited by 8 · see citing works
Capalbo, A., Poli, M., Rienzi, L. F., Girardi, L. D. C., Cimadomo, D., Benini, F., Farcomeni, A., Cuzzi, J., Rubio, C., Albani, E., et al. (2021) · medRxiv · doi:10.1101/2021.02.07.21251201 · Cited by 8 · see citing works
ART and the forgotten siblings: a call for research
Somigliana, E., Parazzini, F., Goisis, A., Esposito, G., Piani, L. L., Filippi, F., & Viganò, P. (2023) · Human Reproduction · doi:10.1093/humrep/dead082 · Cited by 7 · see citing works
Endometrial scratching in Australia, New Zealand and the United Kingdom (UK): a follow-up survey
Sarwari, M., Beilby, K. H., Hammarberg, K., Hickey, M., & Lensen, S. F. (2021) · Human Fertility · doi:10.1080/14647273.2021.1995902 · Cited by 7 · see citing works
Self-citationKang, Y., Wang, Z., Yuan, Y., Liang, H., Duan, X., Gao, Q., & Yin, Z. (2022) · Medicine · doi:10.1097/md.0000000000030150 · Cited by 8 · see citing works
Endometrial receptivity, to test or not to test: the evidence on contemporary assays
Clain, E., & Devine, K. (2022) · F&S Reviews · doi:10.1016/j.xfnr.2022.11.001 · Cited by 7 · see citing works
Fan, Y., Lee, R. W. K., Ng, X. W., Gargett, C. E., & Chan, J. K. Y. (2023) · Scientific Reports · doi:10.1038/s41598-023-27388-8 · Cited by 7 · see citing works
How to deal with time-to-pregnancy data?
Aalberts, J., & van Wely, M. (2023) · Fertility and Sterility · doi:10.1016/j.fertnstert.2023.03.017 · Cited by 7 · see citing works
Why reports of clinical trials should include updated meta-analyses
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Endometrial injury before IVF: light at the end of the tunnel or false hope?
Venetis, C. A. (2020) · Human Reproduction · doi:10.1093/humrep/deaa295 · Cited by 7 · see citing works
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Self-citationEndometrial scratching can be offered outside clinical research setting: let us show you why
Vitagliano, A., Sardo, A. D. S., Noventa, M., Carugno, J. A., Cicinelli, E., Pacheco, L. A., Vitale, S. G., Campo, R., Laganà, A. S., Haimovich, S., et al. (2021) · Human Reproduction · doi:10.1093/humrep/deab060 · Cited by 6 · see citing works
Endometrial scratching: the light at the end of the tunnel
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Survey of in vitro fertilization add-ons in Japan (Izanami project)
Shionoya, N., Yamada, M., Harada, S., Shirasawa, H., Jwa, S. C., Kuroda, K., Harada, M., & Osuga, Y. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1404601 · Cited by 5 · see citing works
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- Authors
- Lensen, S., Osavlyuk, D., Armstrong, S., Stadelmann, C., Hennes, A., Napier, E., Wilkinson, J., Sadler, L., Gupta, D., Strandell, A., Bergh, C., Vigneswaran, K., Teh, W. T., Hamoda, H., Webber, L., Wakeman, S. A., Searle, L., Bhide, P., McDowell, S., Peeraer, K., Khalaf, Y., & Farquhar, C.
- Affiliations
- University of Auckland (NZ)
- Royal Women's Hospital (AU)
- University College Hospital (GB)
- Guy's Hospital (GB)
- From the Department of Obstetrics and Gynaecology, University of Auckland (S.L., D.O., C.F.), and Women’s Health (L. Sadler) and Fertility Plus (D.G., C.F.), Auckland District Health Board, Auckland, Fertility Associates, Christchurch (S.A.W.), and Fertility Associates, Wellington (L. Searle, S.M.) — all in New Zealand; Bath Fertility Centre, Bath (S.A., E.N.), the Department of Medical Statistics, Manchester University NHS Foundation Trust, Manchester (J.W.), and the Department of Obstetrics and...
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2019-01-24
- Volume
- 380
- Issue
- 4
- Pages
- 325-334
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2913330914
- Cited by
- 198
- References
- 43
- Citations by year
- 2026: 14 · 2025: 9 · 2024: 15 · 2023: 28 · 2022: 25 · 2021: 43 · 2020: 39 · 2019: 25
- FWCI
- 31.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion, other-oa)
- Research Explorer (The University of Manchester) (submittedVersion, other-oa)
- ResearchSpace (University of Auckland) (submittedVersion)
- Funders
- Maurice & Phyllis Paykel Trust
- Auckland District Health Board, New Zealand
- Nurture Foundation for Reproductive Health, New Zealand
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Health and Technologies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Assisted Reproductive Technology and Twin Pregnancy
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- endometrial scratching, Pipelle biopsy, in vitro fertilization, live birth, embryo implantation, pregnancy outcomes, procedural pain, frozen embryo transfer, fresh embryo transfer
- MeSH terms
- Adult, Embryo Transfer, Endometrium, Female, Fertilization in Vitro, Humans, Pain Measurement, Pregnancy, Odds Ratio, Treatment Outcome, Live Birth
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