Uterine Scar Healing After Cesarean Section: Managing an Old Surgery in an Evidence-Based Environment

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Does Suture Material Affect Uterine Scar Healing After Cesarean Section? Results from a Randomized Controlled Trial

Cesarean section is one of the most commonly undertaken operations worldwide, and its rate is constantly increasing in recent years both in middle- and high-income countries, despite several scientific societies developing informative campaigns to support vaginal delivery whenever it is possible in order to avoid complications in future pregnancies. Among the most important pieces of evidence about this point, more than 10 years ago the World Health Organization performed a global survey on maternal and perinatal health in Latin America, one of the areas with the highest rate of cesarean section worldwide;¹ this multistage stratified sample comprised 24 geographic regions in eight countries, collecting data from 97,095 deliveries. According to this large cohort analysis, rate of cesarean delivery was positively associated with severe maternal morbidity and mortality, even after adjustment for risk factors; in addition, it was positively associated with a significant increase in fetal mortality rates and higher numbers of babies admitted to intensive care for 7 days or longer, even after adjustment for preterm delivery.

Although cesarean section may be considered as a standardized technique, several different approaches may underlie different outcomes; in 2014, the Cochrane Collaboration published the updates of two interesting systematic reviews and meta-analyses,^2,3 trying to shed new lights about the topic. The first report investigated the effects of nonclosure as an alternative to closure of the peritoneum on intraoperative and immediate- and long-term postoperative outcomes, pooling data from 21 different trials (17,276 women);² while the evidence on long-term pain, adhesion formation, and infertility was limited and inconsistent, the data analysis suggested that nonclosure of parietal peritoneum was associated with a significant reduction of operative time and hospitalization. These elements, together with insufficient evidence of benefit to justify the additional time and use of suture material, lead progressively to consider peritoneal closure after cesarean section as an outdated and unnecessary procedure.

The second report by the Cochrane Collaboration³ was even more groundbreaking, considering the difficult task to provide an evidence-based analysis about different types and methods of performing uterine incision, suture materials, and technique of uterine closure (including single- versus double-layer closure of the uterine incision) on maternal health, infant health, and healthcare resource use. As easy to imagine, the methodological quality of the studies was extremely variable and this (unavoidably) affected the risk of bias assessment, since less than half of the included trials described adequate methods of allocation concealment, and only six trials indicated blinding of outcome assessors. Despite these clear limitations, authors found no statistically significant differences for febrile morbidity following sharp or blunt extension of the uterine incision, whereas the latter was associated with lower mean blood loss and need for blood transfusion; in addition, catgut closure, respect to closure with polygactin, was associated with a significant reduction in the need for blood transfusion and a significant reduction in complications requiring re-laparotomy; finally, single-layer closure of the uterine incision was associated with a reduction in mean blood loss with respect to a double-layer one.

A few years later, the publication of the CORONIS randomized controlled trial's results at 3 years follow-up contributed to a paradigm shift in clinical practice.⁴ In this large study, the authors investigated the rates of pelvic pain, deep dyspareunia, hysterectomy, and outcomes of subsequent pregnancies in women undergoing cesarean section following blunt versus sharp abdominal entry, exteriorization of the uterus for repair versus intra-abdominal repair, single versus double layer closure of the uterus, closure versus nonclosure of the peritoneum, and chromic catgut versus polyglactin-910 for uterine repair. Interestingly and unexpectedly, there was no evidence of a difference in risk of abdominal hernias for blunt versus sharp abdominal entry, no evidence of a difference in risk of infertility or of ectopic pregnancy for exteriorization of the uterus versus intra-abdominal repair, no evidence of a difference in maternal death or a composite of pregnancy complications for single- versus double-layer closure of the uterus, no evidence of a difference in any outcomes relating to symptoms associated with pelvic adhesions such as infertility for closure versus nonclosure of the peritoneum and, finally, no evidence of a difference in the main comparisons for adverse pregnancy outcomes in a subsequent pregnancy for chromic catgut versus polyglactin-910 sutures. In few words, this milestone study seemed to suggest that the type of technique used to perform cesarean section did not influence significantly the medium-to-long term outcomes.

Despite the fact that these studies may be considered conclusive, we had to wait for more recent trials to add new information about the topic; for example, last year Zayed et al.⁵ published the result of a randomized controlled trial about the operative data and the early postoperative outcomes of cesarean sections in which the uterine incision was closed with a barbed suture with those of cesarean sections in which the uterine incision was closed with a conventional smooth suture. As expected, the uterine closure time was significantly lower in barbed suture group; nevertheless, total operative time, mean blood loss, hospitalization, and perioperative complications did not show significant differences between the two groups.

In the same year, another well designed population-based case-control study investigated prelabor and intrapartum risk factors for complete uterine rupture in trial of vaginal birth after a cesarean section (TOLAC) at term, including 39,742 women recorded in the Danish Medical Birth Registry during a 12-year period.⁶ In this study, authors considered all women with a complete uterine rupture as cases (n = 175), and all women with two births with TOLAC at term and no uterine rupture as controls (n = 272). Confirming what was previously reported in the CORONIS trial,⁴ there was no association between single-layer closure and uterine rupture at term.

Despite these interesting data, some concerns remain about the possible technique-related risk factors that may play a significant role in affecting lower uterine segment thickness after cesarean section: this ultrasound-measured parameter is pivotal in the decision-making process, since a value below 2.0 mm between 35 and 38 gestational weeks has been repetitively associated with a greater risk of uterine rupture or scar dehiscence when compared to a measurement greater than 2.0 mm. In this regard, recent data suggest that a double-layer closure of the uterus at previous cesarean is associated with a thicker third-trimester lower uterine segment and a reduced risk of lower uterine segment thickness < 2.0 mm in the next pregnancy, compared to single-layer closure, whereas the type of thread does not seem to have a significant impact.⁷ A well-designed systematic review and meta-analysis⁸ recently confirmed that women who received single-layer closure had a significantly thinner residual myometrial thickness; interestingly, authors found no significant differences in incidence of uterine scar defects (isthmocele), uterine dehiscence, or uterine rupture in the subsequent pregnancy, leaving the debate still open and questioning whether residual myometrial thickness alone could be considered as the main important risk factor for this severe adverse obstetric event.

Regardless of the risk for uterine dehiscence/rupture in the subsequent pregnancy, residual myometrial thickness has also paramount importance to decide the most appropriate surgical approach for the management of isthmocele, a condition that occurs in approximately 60% of patients after a primary cesarean section and 100% after three cesarean sections. As was recently reported in the Consensus Statement by the Global Congress on Hysteroscopy Scientific Committee,⁹ in cases where residual myometrial thickness is greater than 3 mm, hysteroscopic treatment of cesarean-induced isthmocele represents a feasible and safe approach; conversely, when residual myometrial thickness is less than 3 mm, the laparoscopic approach should be favored because of the risk of uterine perforation and bladder injury. In case of hysteroscopic management of isthmocele, this expert Committee suggested to strongly encourage patients to wait at least 3 months after the procedure to conceive, to perform a hysteroscopic follow-up study at 3 months, to visualize surgical outcomes and, as a precautionary measure, recommended delivery by scheduled cesarean section not later than 38 weeks of gestation.

Considering the available evidence and the number of questions still debated about the best surgical approach for cesarean section, the paper recently published in the Journal of Investigative Surgery¹⁰ added a significant piece of evidence to the topic. In this study, the authors showed that the use of synthetic absorbable monofilament sutures for uterine closure was associated with increased residual myometrial thickness measured by transvaginal ultrasound 6–9 months after birth, with respect to synthetic absorbable multifilament sutures. As a indirect consequence of this result, monofilament sutures may improve uterine scar wound healing without increasing costs, operation time, or intraoperative complication rates. From a speculative point of view, the increased residual myometrial thickness may be associated with a reduced incidence of isthmocele: since Di Spiezio Sardo et al.⁸ did not find significant differences for this parameter between women that underwent single-layer versus double-layer uterine closure, probably the use of different suture material is the actual key determinant.

DECLARATION OF INTEREST

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.