Fertility and reproductive outcomes following high‐energy pelvic fractures: A systematic review and meta‐analysis

There is a need to decipher the effect of pelvic fractures (PFs) upon female fertility and live birth rate, as data including treatment regimens in large, unselected populations remain scarce.

delivery they will have. Nonetheless, PFs had no discernible effect on miscarriage or fertility, according to Copeland et al. 3 Moreover, sexual health can be significantly affected, with patients often reporting dyspareunia and urinary problems. 1 Cannada and Barr 4 showed that in a cohort of 233 women with PFs, 45% of women reported feeling less sexually attractive, 39% reported having less sexual pleasure, and 45% reported being less interested in sexual intercourse.
The management of PFs is frequently contentious. Non-surgical treatment can be used for non-displaced or minimally displaced fractures; however, surgical treatment often remains the preferred option for displaced PFs. 5 Even though studies have shown that PFs can affect the mode of delivery, vaginal delivery (VD) still has an important role in the delivery of these patients. Studies have reported variable rates of cesarean section (CS) following PFs ranging from 8% to 66%. 4,6,7 A recent large nationwide registry study showed that despite the greater likelihood of CS among women with a previous pelvic fracture, VD may still be a viable option. 8 There is a dire need to further decipher the effect of PF upon female fertility and live birth rate, as data including treatment regimens in large, unselected populations, remain scarce. To date, only a few modest studies have looked at live births and pregnancies following PFs. Additionally, information on comorbidities, mechanisms of damage, specific fracture types, and surgical fixation approaches seems to be lacking. To the best of our knowledge, this is the first systematic review to evaluate infertility and reproductive outcomes following a high-energy PF.  included human participants and English language articles. The following search term was used in OVID: (pelvic fracture* or pelvic ring fracture* or pelvic injury).ti. AND (sexual dysfunction or infertility or urogenital trauma or childbearing or pregnancy or fertility or assisted reproduction).ti.ab. limit to (English language and humans and female). No geographical or age restrictions were applied. The same search strategy was adapted for the remaining databases. The systematic review was not prospectively registered.

| Inclusion and exclusion criteria
All included studies (retrospective) examined the effect of pelvic fractures upon observed percentage live birth rate (VD and CS) within the time of follow up as defined per study (Table 1).
Excluded studies and justifications are recorded in Table S1.

| Data extraction
After removing duplicates, citations were screened by title and abstract, then full texts were appraised to determine their eligibility by three authors (SK, JE, GK) ( Figure 1). Two authors (GK, SK) independently conducted the abstract and full-text screening.
Disagreements were resolved by a consensus meeting and thirdauthor participation (JE). Peer-reviewed full-text papers that reported live birth outcomes were selected.

| Outcomes
The aim of the present study was to assess the effect of high energy PFs upon female fertility and live birth rate. The primary outcome of this study was to identify the rate of live births and mode of delivery in patients of childbearing age following a pelvic fracture. Secondary

| Quality assessment
The quality of the included studies was assessed by three independent reviewers (SK, JE, GK) using the Newcastle-Ottawa Scale (NOS) for observational studies. 12 As per NOS assessment approach, a study could be awarded a maximum of one star for each numbered item within the "selection" and "exposure" categories. A maximum of two stars could be given for the "comparability" element. Studies were of high quality, if they had a NOS score of 6 or more. Domains were scored by SK, JE, and GK and study-level NOS score was defined as low risk of bias, when all domains received low bias scores unanimously. 12

| Data analysis
All relevant information was extracted and formatted appropriately to allow for quantitative analysis. Statistical analysis was performed using Graphpad prism (v. 9) (GraphPad, San Diego, CA, USA).
Descriptive statistics and unpaired, t test (Welch test) were employed for data rationalization and statistical significance analysis.

| Data synthesis and meta-analysis
Clinical, study context and design were compared and in those where studies were considered suitably homogeneous for pooling. 13 The meta-analysis of studies regarding dyspareunia and infertility outcomes was conducted by computing the HR from the original data by Generic Inverse Variance analysis with review manaGer (revman) v5.4 software using a random-effect model. Statistical heterogeneity was quantified using I 2 statistics and Cochrane Q tests.

| Publication bias
Asymmetry was assessed by funnel plot, and asymmetry was assessed formally by rank correlation test (Begg test; revman V. 5.4). 14 Sensitivity analyses were conducted to assess the impact of individual potential confounding variables.

| Study characteristics
A total of six retrospective studies were deemed eligible for inclusion in the present systematic review. One study was deemed of good quality, 8
Interestingly, albeit not widely reported across studies, only half of the participants in the Copeland et al. 3 study were given information or recommendations regarding future ability to bear children.
In the Cannada and Barr 4 study, up to 29% (n = 20) of the patients reported that they were afraid to get pregnant following their accident. Intriguingly, there was a distinct differentiation among patient cohorts' mode of delivery before and after 2000 (Figure 2b,c  (Figure 2c).

| DISCUSS ION
To the best of our knowledge, this is the first systematic review to evaluate infertility and reproductive outcomes following a It is estimated that 3%-4.3% of skeletal trauma is comprised Although high-energy PF injuries appear to be increasing among female patients of childbearing age, a consistent multidisciplinary approach, including orthopedic and obstetric consultations, does not appear to be the norm. The increased risk of VD complications following a PF injury appears to be presumed rather than thoroughly evaluated through multidisciplinary and patient discussions. 8 It has been demonstrated that pregnant women are willing to accept higher complication risks associated with VD in contrast to the treating clinicians who were shown to be more likely to resort to CS for themselves or their partners. 25 In contrast, the incidence of operative complications including major bleeding, postoperative wound and urinary tract infections as well as prolonged recovery period and neonate adverse outcomes in CS are significantly higher than those of PV deliveries. 26,27 Due to the lack of consensus and guideline- pregnancy as well as patient-reported fear of pregnancy should also be included as outcomes, to educate future clinical and psychological support required for this population.
This systematic review did not explore the disabilities that women suffered after PFs, which can affect the mode of delivery.
Pelvic fractures affecting adduction, abduction, flexion, and extension at the hip joints can prevent vaginal delivery but PFs not affecting pelvic joint movements may not have any effect on the mode of delivery. Additionally, PFs not causing pelvic hematomas, uterine lacerations, or major surgical interventions in the pelvic region may not affect fertility. Lastly, the increase in CS rate after 2000 in women with PFs may be due to obstetric causes not related to PFs.
Overall, findings of the present systematic review, suggest that there are no significant differences of live birth, infertility, and dyspareunia rates across patients with PFs in comparison to non-PF patients. Nonetheless, the CS rates across this patient population appear to be increasing. The clinical indication for this trend remains to be elucidated in future large-scale studies.

AUTH O R CO NTR I B UTI O N S
SLK and JE contributed to study conception and design; SLK, JE, and GK contributed to data collection; SLK, JE, GK, and ID contributed to analysis and interpretation of results and draft manuscript preparation. All authors reviewed the results and approved the final version of the manuscript.

CO N FLI C T O F I NTE R E S T
The authors do not have any competing interests to disclose.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from the corresponding author upon reasonable request.