The impact of uterine septum on reproductive outcome—half-empty or half-full?

Few clinical dilemmas in reproductive medicine have persisted over decades with little progress toward resolution. The impact of a uterine septum on reproductive outcome is one of the most important and, regrettably, one of the thorniest dilemmas, for a variety of reasons so familiar to us. First, our ability to diagnose anomalies by combinations of imaging and endoscopy has been possible for only a short time. Indeed, not all that many years ago, the literature included a number of studies that almost certainly overstated the prevalence and impact of bicornuate uteri that were more likely to have been septate (Ludmir J. Samuels P. Brooks S. Mennuti M.T. Pregnancy outcome of patients with uncorrected uterine anomalies managed in a high-risk obstetric setting.). Second, the problem of diagnostic inaccuracy has been exacerbated by the lack of universally accepted and standard descriptive terms. Many women diagnosed with a septum according to European definitions (Grimbizis G.F. Gordts S. Di Spezio Sardo A. Brucker S. De Angelis C. Gergolet M. et al.The ESHRE-ESGE consensus on the classification of female genital tract congenital anomalies.) would be characterized as having an arcuate or even a normal uterus in the United States. Third, the importance of various characteristics of the septum often goes unaddressed. For example, we have long acknowledged that a larger septum may have more clinical impact than a small one, but we have considered other factors, such as vascularity or cytoarchitectural features, with less clarity.

We are fortunate that our battlers agree on several key themes, which allows the dispute to focus on the weight and interpretation of the evidence rather than on discordant assumptions. Both sides stipulate that existing data from studies of infertility and uterine septa generally suffer mightily from ascertainment bias. They further agree that the lack of uniform diagnostic criteria and the absence of a standardized surgical approach are important confounders in the interpretation of the existing data. Both sides concur that existing clinical trial designs used in studies of recurrent miscarriage almost all suffer from the absence of a control group or the common shortcoming of using the patient as her own control. Finally, they both acknowledge that the surgical procedure itself is not likely to result in significant perioperative complications, thereby avoiding the overly simplistic argument that the evidence for surgery must be compelling to merit a foray into the operating room.

How then to build a compelling case for either expectant or surgical management? Alvero and colleagues strongly argue that the burden of proof should be borne by those who advocate intervention—a fair opening salvo. They are unconvinced that existing data support an association between a uterine septum and infertility and are similarly skeptical about the impact of a septum on recurrent pregnancy loss. They cite data suggesting that most of the women with a septum do not suffer a pregnancy loss, and they present the results of a recently published prospective trial showing that women undergoing septum resection have outcomes similar to those managed expectantly (Rikken J.F.W. Kowalik C.R. Emanuel M.H. Bongers M.Y. Spinder T. Jansen F.W. et al.Septum resection versus expectant management in women with a septate uterus: an international multicentre open-label randomized controlled trial.). Their strategy is to seek the high ground, concluding that the best answer is unknowable at present, given the limitations of existing studies. Rather than settling for a surgical approach that is not clearly supportable, they advocate for a prospective registry predicated on meticulous definitions of findings and features of a uterine septum. One would hope that this approach would produce crisp diagnostic characterization that would ultimately lead to robust, well-designed trials that provide clear direction to clinicians.Burney and colleagues mount their argument in favor of septum resection with surgical incisiveness and purpose. They parry the ambivalence about the association between the presence of a septum and infertility with epidemiologic data that they believe show a conclusive link between the two. They buttress their argument with in vitro fertilization data that they believe provide definitive evidence that a septum is an independent factor that causes reduced pregnancy rates (Tomazevic T. Ban-Frangez H. Virant-Klun I. Verdenik I. Pozlep B. Vrtacnik-Bokal E. Septate, subseptate and arcuate uterus decrease pregnancy and live birth rates in IVF/ICSI.). They use additional evidence from this and other studies to support their further argument that resection restores reproductive normalcy. The Burney team is similarly undeterred by the hesitancy of team Alvero in accepting that existing evidence shows a causative association between a uterine septum and pregnancy loss. Their strategy includes a final potential coup de grâce that addresses the impact of a septum on obstetrical outcome in women who conceive successfully. They cite studies reporting that women with a septum have increased risks of preterm labor, malpresentation, growth restriction, placental abruption, and overall perinatal mortality. We may speculate that their answer to the initial challenge of providing the burden of proof in favor of surgery relates neither to infertility nor to miscarriage, but rather rests on the best way to assure the birth of a healthy baby at term.

And where do the armies of clinicians find themselves after this well-waged battle of convincing intellectual antagonists? The easy answer is to follow the arguments that have successfully won them over. However, we should appreciate that even the most decisive among us will recognize that neither side clearly owns the entire weight of evidence. It is likely that many of us will find components of both sides to embrace—perhaps a prospective registry that includes careful attention to obstetrical outcomes is a valuable component of the short-term answer? At the end of this Fertile Battle, I wonder if the dilemma for today’s clinicians comes down to deciding whether expectant management is the better choice in the absence of compelling data, or if one should choose to resect the septum because doing so might provide benefit without exposing the patient to significant surgical risk. Is the cup half-empty or half-full?

ReferencesLudmir J. Samuels P. Brooks S. Mennuti M.T.

Pregnancy outcome of patients with uncorrected uterine anomalies managed in a high-risk obstetric setting.

Obstet Gynecol. 75: 906-910Grimbizis G.F. Gordts S. Di Spezio Sardo A. Brucker S. De Angelis C. Gergolet M. et al.

The ESHRE-ESGE consensus on the classification of female genital tract congenital anomalies.

Gynecol Surg. 10: 199-212Rikken J.F.W. Kowalik C.R. Emanuel M.H. Bongers M.Y. Spinder T. Jansen F.W. et al.

Septum resection versus expectant management in women with a septate uterus: an international multicentre open-label randomized controlled trial.

Hum Reprod. 36: 1260-1267Tomazevic T. Ban-Frangez H. Virant-Klun I. Verdenik I. Pozlep B. Vrtacnik-Bokal E.

Septate, subseptate and arcuate uterus decrease pregnancy and live birth rates in IVF/ICSI.

Reprod Biomed Online. 21: 700-705Article InfoPublication History

Published online: July 03, 2021

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You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/posts/33220

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DOI: https://doi.org/10.1016/j.fertnstert.2021.06.010

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©2021 American Society for Reproductive Medicine, Published by Elsevier Inc.

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