Hysteroscopy in recurrent in-vitro fertilisation failure (TROPHY): a multicentre, randomised controlled trial

http://thelancet.com/journals/lancet/article/PIIS0140-6736%2816%2900258-0/abstract

Dr Tarek El-Toukhy, MRCOG

,

Rudi Campo, MD

,

Yacoub Khalaf, FRCOG

,

Carla Tabanelli, MD

,

Luca Gianaroli, MD

,

Sylvie S Gordts, MD

,

Stephan Gordts, MD

,

Greet Mestdagh, MD

,

Tonko Mardesic, MD

,

Jan Voboril, MD

,

Gian L Marchino, MD

,

Prof Chiara Benedetto, MD

,

Talha Al-Shawaf, FRCOG

,

Luca Sabatini, MRCOG

,

Paul T Seed, MSc CStat

,

Marco Gergolet, MD

,

Prof Grigoris Grimbizis, MD

,

Hoda Harb, PhD

,

Prof Arri Coomarasamy, FRCOG

Published Online: 27 April 2016

DOI: http://dx.doi.org/10.1016/S0140-6736(16)00258-0

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Article Info

• Summary
• Full Text
• Tables and Figures
• References

Summary

Background

The success rate of in-vitro fertilisation (IVF) remains low and many women undergo multiple treatment cycles. A previous meta-analysis suggested hysteroscopy could improve outcomes in women who have had recurrent implantation failure; however, studies were of poor quality and a definitive randomised trial was needed. In the TROPHY trial we aimed to assess whether hysteroscopy improves the livebirth rate following IVF treatment in women with recurrent failure of implantation.

Methods

We did a multicentre, randomised controlled trial in eight hospitals in the UK, Belgium, Italy, and the Czech Republic. We recruited women younger than 38 years who had normal ultrasound of the uterine cavity and history of two to four unsuccessful IVF cycles. We used an independent web-based trial management system to randomly assign (1:1) women to receive outpatient hysteroscopy (hysteroscopy group) or no hysteroscopy (control group) in the month before starting a treatment cycle of IVF (with or without intracytoplasmic sperm injection). A computer-based algorithm minimised for key prognostic variables: age, body-mass index, basal follicle-stimulating hormone concentration, and the number of previous failed IVF cycles. The order of group assignment was masked to the researchers at the time of recruitment and randomisation. Embryologists involved in the embryo transfer were masked to group allocation, but physicians doing the procedure knew of group assignment and had hysteroscopy findings accessible. Participants were not masked to their group assignment. The primary outcome was the livebirth rate (proportion of women who had a live baby beyond 24 weeks of gestation) in the intention-to-treat population. The trial was registered with the ISRCTN Registry, ISRCTN35859078.

Findings

Between Jan 1, 2010, and Dec 31, 2013, we randomly assigned 350 women to the hysteroscopy group and 352 women to the control group. 102 (29%) of women in the hysteroscopy group had a livebirth after IVF compared with 102 (29%) women in the control group (risk ratio 1·0, 95% CI 0·79–1·25; p=0·96). No hysteroscopy-related adverse events were reported.

Interpretation

Outpatient hysteroscopy before IVF in women with a normal ultrasound of the uterine cavity and a history of unsuccessful IVF treatment cycles does not improve the livebirth rate. Further research into the effectiveness of surgical correction of specific uterine cavity abnormalities before IVF is warranted.

Funding

European Society of Human Reproduction and Embryology, European Society for Gynaecological Endoscopy.


http://thelancet.com/journals/lancet/article/PIIS0140-6736%2816%2900231-2/abstract

Hysteroscopy before in-vitro fertilisation (inSIGHT): a multicentre, randomised controlled trial

Janine G Smit, MD

,

Jenneke C Kasius, PhD

,

Prof Marinus J C Eijkemans, PhD

,

Carolien A M Koks, PhD

,

Ronald van Golde, PhD

,

Annemiek W Nap, PhD

,

Gabrielle J Scheffer, PhD

,

Petra A P Manger, PhD

,

Annemieke Hoek, PhD

,

Benedictus C Schoot, PhD

,

Arne M van Heusden, PhD

,

Walter K H Kuchenbecker, PhD

,

Denise A M Perquin, PhD

,

Kathrin Fleischer, PhD

,

Eugenie M Kaaijk, PhD

,

Alexander Sluijmer, PhD

,

Jaap Friederich, PhD

,

Ramon H M Dykgraaf

,

Marcel van Hooff, PhD

,

Leonie A Louwe, MD

,

Janet Kwee, PhD

,

Corry H de Koning

,

Ineke C A H Janssen, PhD

,

Femke Mol, PhD

,

Prof Ben W J Mol, PhD

,

Prof Frank J M Broekmans, PhD

,

Helen L Torrance, PhD

Published Online: 27 April 2016

DOI: http://dx.doi.org/10.1016/S0140-6736(16)00231-2

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Article Info

• Summary
• Full Text
• Tables and Figures
• References
• Supplementary Material

Summary

Background

Hysteroscopy is often done in infertile women starting in-vitro fertilisation (IVF) to improve their chance of having a baby. However, no data are available from randomised controlled trials to support this practice. We aimed to assess whether routine hysteroscopy before the first IVF treatment cycle increases the rate of livebirths.

Methods

We did a pragmatic, multicentre, randomised controlled trial in seven university hospitals and 15 large general hospitals in the Netherlands. Women with a normal transvaginal ultrasound of the uterine cavity and no previous hysteroscopy who were scheduled for their first IVF treatment were randomly assigned (1:1) to either hysteroscopy with treatment of detected intracavitary abnormalities before starting IVF (hysteroscopy group) or immediate start of the IVF treatment (immediate IVF group). Randomisation was done with web-based concealed allocation and was stratified by centre with variable block sizes. Participants, doctors, and outcome assessors were not masked to the assigned group. The primary outcome was ongoing pregnancy (detection of a fetal heartbeat at >12 weeks of gestation) within 18 months of randomisation and resulting in livebirth. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01242852.

Findings

Between May 25, 2011, and Aug 27, 2013, we randomly assigned 750 women to receive either hysteroscopy (n=373) or immediate IVF (n=377). 209 (57%) of 369 women eligible for assessment in the hysteroscopy group and 200 (54%) of 373 in the immediate IVF group had a livebirth from a pregnancy during the trial period (relative risk 1·06, 95% CI 0·93–1·20; p=0·41). One (<1%) woman in the hysteroscopy group developed endometritis after hysteroscopy.

Interpretation

Routine hysteroscopy does not improve livebirth rates in infertile women with a normal transvaginal ultrasound of the uterine cavity scheduled for a first IVF treatment. Women with a normal transvaginal ultrasound should not be offered routine hysteroscopy.

Funding

The Dutch Organisation for Health Research and Development (ZonMW).