3D ultrasound is recommended for the detection of Müllerian uterine malformations that are associated with RPL. With 3D ultrasound, several other uterine abnormalities can be seen. This chapter will explore treatment options for Müllerian uterine malformations that can improve the chances of a live birth in women with RPL, but we will also elaborate briefly on treatment options for other abnormalities.

ESHRE Guideline group on RPL (2022) 

Summary of literature

Reconstructive surgery is a treatment option for congenital uterine malformations, but it depends on the type and the severity of the malformation.

Septate uterus

For a septate uterus, hysteroscopic metroplasty has become the indicated treatment of choice (Valle and Ekpo, 2013). Older studies have discussed abdominal metroplasty, but based on lower morbidity, ease of the procedure and the reduced risk of intrauterine adhesions, hysteroscopic metroplasty is the preferred option, and widely applied (Grimbizis et al., 2001, Mollo et al., 2011, Valli et al., 2004,).

One meta-analysis of 7 comparative studies involving women with uterine septum and a history of subfertility and/or poor reproductive outcomes showed that hysteroscopic septum resection reduced the rate of pregnancy loss (Krishnan et al. 2021). The women treated by hysteroscopic septum resection had a lower rate of pregnancy loss compared with women with conservative management (OR .25, 95%CI 0.07-0.88). However, no significant effect was seen on live birth, clinical pregnancy rate or preterm delivery.

A more recent meta-analysis showed also that hysteroscopic metroplasty reduced the risk of pregnancy loss in patients with complete uterine septum (OR 0.16, 95%CI0.03-0.78) or partial uterine septum (OR 0.36 (95% CI 0.19-0.71) (Carrera et al. 2021). The clinical pregnancy rates, the live birth rates and the risk of caesarean delivery were not significantly different between the treated and untreated group.

A meta-analysis (not specific for RPL) reported a significantly decreased risk of pregnancy loss in women who underwent hysteroscopic septotomy as compared to women who did not undergo treatment (RR 0.37; 95% CI 0.25-0.55; I2 = 0%; five studies) (Venetis et al., 2014).

A prospective study reported pregnancy outcomes in women with RPL (≥ 2 PLs) and uterine malformations. Of the 124 women with a septate uterus, 109 underwent surgery. In women that achieved pregnancy, 78 of 96 (81.3%) women treated with surgery and 8 of 13 (61.5%) women without surgery delivered a live born at the first pregnancy after examination (Sugiura-Ogasawara et al., 2015). There were no significant differences in preterm birth, low birth weight or caesarean section

Non-controlled and observational studies have suggested a beneficial effect of surgery (Homer et al., 2000) but are biased by comparing miscarriage rates before and after treatment. Furthermore, most of them describe women with RPL as a small subgroup. One of the largest study on 63 women with RPL and septate uterus reported a decrease in the miscarriage rate from 90% to 10-20% after surgery (Porcu et al., 2000).

Recent data from the TRUST trial, comparing 79 women with a septate uterus, showed no evidence for benefit from septum resection in term of pregnancy loss (RR 2.3, 95% CI 0.86–5.9), clinical pregnancy (RR 1.2, 95%CI 0.77–1.2), ongoing pregnancy (RR 0.95, 95%CI 0.52–1.8), live birth (RR 0.88, 95% CI 0.47–1.7) or preterm birth (RR 1.3, 95% CI 0.37–4.4) rates (Rikken et al. 2021). Similar results were obtained in an earlier large cohort study and showed that septum resection does not lead to improved reproductive outcomes compared to expectant management for women with a septate uterus (Rikken et al. 2020).

Although a reduction in the miscarriage rate in 72 women with RPL and septate uterus was reported in the study of Venturoli, they also reported on pregnancies and deliveries. They found that surgery had a negative impact on fertility, with only 52% becoming pregnant in the first year after surgery. For those becoming pregnant, they found a reduction in the miscarriage rate (Venturoli et al., 2002).

Hysteroscopic treatment of a symptomatic septate uterus can be accomplished via various methods including hysteroscopic scissors, and electrosurgical electrodes fitted through the hysteroscope (or resectoscope), which are the most common used methods. There is no evidence to elect one method over the others (Colacurci et al., 2007, Valle and Ekpo, 2013). However, the efficiency of such treatment for septum resection has not been defined as most studies do not have a follow up hysteroscopy to compare before and after treatment, and there are no objective morphometric parameters.

Other uterine malformations

For hemi-uterus (former AFS unicornuate uterus), uterine reconstruction is not feasible (Jaslow, 2014). However, in cases of hemi-uterus with rudimentary horn and cavity, laparoscopic removal of the rudimentary horn should be considered to avoid “ectopic” pregnancy in this cavity and, in some cases, hematocavity (obstructive symptoms).

Metroplasty (transabdominal or laparoscopically) is the only option for a bicornuate uterus (Papp et al., 2006, Alborzi et al., 2015). Surgery however showed no benefit for having a live born in women with a bicornuate uterus, but tended to decrease the preterm birth rate and the low birth weight in women with RPL (Sugiura-Ogasawara et al., 2015). Overall, there is no strong evidence in favor of metroplasty in women having RPL and a bicornuate uterus (Bailey et al., 2015).

In women with RPL and bicorporeal uterus and double cervix (former AFS didelphic uterus), laparoscopic unification of the uterus has been described, but the efficacy for improving live birth rate, is unclear as the data are based on few studies and few patients (Alborzi et al., 2009 and 2015, Jaslow, 2014).

We found no evidence supporting any recommendations on treatment of T-shaped uterus or bicorporal septate uterus in women with RPL.

Recommendations

Justifications 

Women with (untreated) congenital uterine malformations have significantly impaired pregnancy outcome (see also chapter 8) (adaptation part D, chapter 6) (Grimbizis et al., 2001).

For women with RPL and septate uterus, several meta-analyses of low quality studies showed a benefit of treatment in reducing the miscarriage rate: women who underwent hysteroscopic septum resection had a significantly decreased probability of pregnancy loss compared with women who did not undergo treatment. There was no effect on the clinical pregnancy rate and live birth rate. However, an international, multicentre, open label, randomized controlled trial showed that septum resection does not improve the reproductive outcomes in treated women (Rikken et al. 2021). Larger randomized controlled trials are still needed to demonstrate a clear benefit of hysteroscopic septum resection.  Therefore, the guideline development group decided to formulate a conditional recommendation base on low quality evidence in favor of hysteroscopic septum resection to reduce the rate of pregnancy loss.

For Müllerian malformations other than septate uterus, there are currently no high quality studies to support surgery for improving the live birth rate or decreasing the miscarriage rate. Existing studies are difficult to summarize as they use different diagnostic criteria, various techniques, different endpoints, and a wide range of therapeutic options (transabdominal, hysteroscopic metroplasty by using monopolar, bipolar, loop, or scissors).

To establish the value of metroplasty for bicorporeal uterus with normal cervix (former AFS bicornuate uterus) conclusively, controlled trials comparing women after surgery with matched controls undergoing expectant management are needed. Furthermore, the risk of subfertility after surgery should be clarified. For other Müllerian malformations, good quality randomized trials with carefully classified patients are urgently needed (Sugiura-Ogasawara et al., 2013).

Additional information

In the event of irreparable anatomic uterine abnormalities and RPL, IVF with transfer of embryos to an appropriately selected gestational carrier (surrogacy) can be an option.

More information on the ESHRE/ESGE classification system of female genital tract congenital malformations (Grimbizis, 2013) is available on the ESHRE website (www.eshre.eu/guidelines)

References
The references for this submodule can be found here.

The results of the summary of literature were adapted from the international ESHRE guideline Recurrent Pregnancy Loss (2022). More details about the methodology of the ESHRE guideline on RPL (2022) can be found in “Annex 5: Methodology” of the ESHRE guideline and in the Manual for ESHRE guideline development, version 2013, which can be consulted at the ESHRE website. The evidence tables and literature studies can be found at the ESHRE website in Supplementary data files.