No evidence that septum resection improves reproductive outcomes

Hysteroscopic resection is standard practice in treating women with a septate uterus.

Published 05 May 2021

A randomised trial has confirmed earlier cohort study findings that septum resection in women with a septate uterus and a history of subfertility has no advantages over expectant management in improving live birth rates. Is there now any rationale behind surgery, ask the authors?

Surgical removal of the septum in women with a septate uterus has no benefit in improving live birth rates or other reproductive outcomes, and cannot be recommended as a routine procedure. That’s the clear message from the authors of the first and much-anticipated randomised trial of hysteroscopic metroplasty, which concludes that the procedure lacks ‘any evidence of effectiveness’ and has ‘potential for harm’.(1)

The TRUST (The Randomised Uterine Septum Trial) study of 79 women found that live birth within 12 months of randomisation occurred in 31% (12 out of 39) of those allocated to septum resection vs 35% (14 out of 40) of those who underwent expectant management.

A single uterine perforation out of the 39 procedures (2.6%) occurred after hysteroscope introduction although the septum was removed four weeks later without complications.

Until now, there has been no robust evidence to establish the effectiveness of surgical removal of the septum in improving reproductive outcomes. Nevertheless, hysteroscopic resection is standard practice for treating women with a septate uterus, the most common congenital uterine abnormality. The condition affects up to an estimated 2% of women of reproductive age and puts them at increased risk for subfertility, recurrent miscarriage and preterm birth.

Surgical resection is recommended in an ASRM guideline on septate uterus management (grade C evidence) but is not supported by ESHRE, the National Institute for Health and Care Excellence (NICE), and the Royal College of Obstetricians and Gynaecologists (RCOG); a Cochrane review in 2017, performed by most of those involved in the TRUST study, concluded that RCTs were needed urgently into the safety and benefits of surgery.(2,3)

TRUST’s lead author, Judith Rikken from AMC Amsterdam, was also behind a large (n=257) cohort study published last year which concluded resection appeared neither to prevent pregnancy loss nor preterm birth, and led to surgical complications in 5% of subjects.(4)

To provide now what they describe as a ‘higher level of evidence’, Rikken and colleagues performed an international, multicentre, open-label RCT in 10 hospitals in four countries (Netherlands, UK, USA and Iran) between October 2010 and September 2018 to compare hysteroscopic resection with expectant management.

A total of 80 women wishing to become pregnant and with a history of subfertility, pregnancy loss or preterm birth were randomly assigned to resection or expectant management. One woman was subsequently excluded from the resection group after she withdrew informed consent.

The expectant management group received no specific intervention but were advised to continue trying to conceive naturally or with ART, and participants with recurrent pregnancy loss and co-existing antiphospholipid syndrome were allowed aspirin/heparin.

The primary outcome was conception leading to live birth (a living foetus beyond 24 weeks gestation) within 12 months after randomisation, and women who conceived were followed for the duration of pregnancy.

The TRUST findings demonstrate that the benefit the authors had anticipated in live birth rate from surgery (70% surgery vs 35% expectant management) based on the results of retrospective studies can now be ruled out in a mixed study population. There was no evidence of a difference in clinical pregnancy, ongoing pregnancy, pregnancy loss or preterm birth rates. However, sample size was a limitation of the study along with recruitment. Indeed, the authors say the latter – as with many RCTs today - presents a challenge for adequately powering a worldwide trial to confirm or refute their findings.

So how should patients with septate uterus now be managed in light of the TRUST results? The authors say they should be informed about the study data and receive counselling after which ‘an informed decision can then be made’.

An accompanying editorial in Human Reproduction poses – but does not answer – the question of whether hysteroscopic septum resection should be banned outright.(5) However, the comment authors do say that ‘septoplasty will be put under scrutiny all over the world’ thanks to the efforts of Rikken and colleagues, and their findings may encourage more women and surgeons to participate in new RCTs.

1. Rikken J, Kowalik C, Emanuel M, et al. Septum resection versus expectant management in women with a septate uterus: an international multicentre open-label randomized controlled trial. Hum Reprod 2021; 36; 1260 -1267;
2. Practice Committee of the ASRM. Uterine septum: a guideline. Fertil Steril 2016; 106: P530-540.
3. Rikken JFW, Kowalik CR, Emanuel MH, et al. Septum resection for women of reproductive age with a septate uterus. Cochrane Database of Systematic Reviews 2017.
4. Rikken J, Verhorstert K, Emanuel M, et al. Septum resection in women with a septate uterus: a cohort study. Hum Reprod 2020; 35: 1722-1722.
5. Vercellini P, Chiaffarino F, Parazzini F. ‘It’s all too much’: the shadow of overtreatment looms over hysteroscopic metroplasty for septate uterus. Hum Reprod 2021; doi:10.1093/humrep/deab081

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