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Abstract
Objective This systematic review and meta-analysis were aimed to summarize the body of evidence on the prognosis after laparoscopic surgeries for pathological conditions on distal oviducts, then, furthermore, to evaluate prognostic factors for pregnancy outcomes.
Methods We conducted a systematic review and meta-analysis to summarize the body of evidence on this topic, with the review question formulated as “what is the prognosis after the laparoscopic fimbrioplasty, salpingostomy, or salpingoneostomy for patients with pathologic conditions on the distal oviducts.” We searched Medline and EMBASE on June 1st, 2020. Two investigators (HH and ZY) independently screened the references of all retrieved records for potentially eligible studies by firstly, through titles and abstract, and then full-text. A study would be included if it was a primary study reporting pregnancy outcomes of patients after laparascopic surgery. A meta-analysis of the rates of pregnancy, ectopic pregnancy, live birth, and miscarriage was performed using a random effect model.
Results We identified 3861 records and included 21 reports with 2473 participants. The pooled estimate for the pregnancy rate was 35.1% (95% CI: 30.7%–39.7%, I2 = 78%, low certainty). The pooled estimates for the live birth rate, ectopic pregnancy rate, and miscarriage were 24.4% (95% CI: 20.2%–28.8%, I2 = 58%; 1154 participants; low certainty), 6.2% (95% CI: 4.4%–8.2%, I2 = 61%; 2363 participants; low certainty), and 4.6% (95% CI: 2.8%–6.9%, I2 = 10%; 544 participants; low certainty). Our analyses suggested that the more damaged tubal was associated with a decreased pregnancy rate, and patients with moderate or severe adhesion had lower pregnancy rates compared with patients with mild pelvic adhesion.
Conclusion We estimated the pregnancy rate, ectopic pregnancy rate, and miscarriage rate of patients with distal tubal pathology after the laparoscopic fimbrioplasty or salpingostomy. Low certainty evidence suggested that laparoscopic surgery can restore the tubal function and cure infertility and should be considered as an alternative to in vitro fertilization. Tubal damage stage and adhesion are associated with worse pregnancy outcomes.
- Fallopian tube disease
- Laparoscopy
- Fimbrioplasty
- Salpingostomy
- Salpingoneostomy
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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1 Introduction
The pathologic conditions on distal fallopian tube include hydrosalpinxes and fimbrial phimosis. Hydrosalpinx refers to a condition that the tube is completely occluded, which is characterized by a distally blocked fallopian tube filled with fluid while fimbrial phimosis refers to a narrow phimotic tubal opening resulted from fimbrial agglutinative adhesions. Tubal diseases account for 25%–35% of female infertilities, of which the pathologic conditions on distal fallopian tube is a major part. Empirical studies suggested that pathologic conditions on distal fallopian tube decrease the rate of fertilized-egg implantation and pregnancy rate. Patients with distal-tubal-problem related infertility can choose assisted reproductive technology. However, surgical correction can also restore the tubal structure or function and cure infertility. Therefore, it is an alternative to assisted reproductive technology. Laparoscopic fimbrioplasty is an operation to treat phimosis on the incompletely obstructed distal part of the tube, whereas salpingostomy and salpingoneostomy are the surgical techniques to restore the tubal function via opening the distally occluded end.
Surgical correction may be a cost-effective alternative to assisted reproductive technology, such as in vitro fertilization (IVF) [1]. Healthcare providers should understand the prognosis after surgeries, the time to pregnancy after treatment, and prognostic factors, cost of treatment, and patient preferences to make an informed decision [2]. There have been multiple reports on the effects of the surgical correction on pregnancy outcomes [3–6]. However, previous reports were mostly on the results from a single institution, and the pregnancy outcomes also depend on the surgeons’ expertise and experience or the technical standards of local institutions. Moreover, treatment in previous reports may not represent the state of arts. Along with the evolvement of technology, assisted reproductive technology gains popularity. It is relevant to consider the latest evidence on laparoscopic surgeries in the current setting [7]. Furthermore, it is crucial to review and analyze all pregnancy-related outcomes including intrauterine pregnancy, ectopic pregnancy, miscarriage, and live birth. Since the systematic review method is effective in summarizing the body of evidence on prognosis, this systematic review and meta-analysis aimed to summarize the body of evidence on the prognosis after laparoscopic surgery treatment of the pathologic conditions in the distal fallopian tube, and to evaluate prognosis factors for pregnancy outcomes.
2 Methods
We conducted this systematic review and meta-analysis to answer the research question “what is the prognosis after the laparoscopic fimbrioplasty or salpingostomy for patients with pathologic conditions on the distal oviducts.” The systematic review with meta-analysis was registered on PROSPERO (CRD42018084496). Ethical approval was not applicable because all the work was developed using published data.
2.1 Study selection and outcome measures
A team worked out the inclusion and exclusion criteria to identify eligible studies for the research question. Based on the criteria, we included studies if they were 1) primary studies, 2) on laparoscopic surgeries as either fimbrioplasty or salpingostomy (with or without adhesiolysis) purposed to preserve or restore the tubal function, 3) for patients with laparoscopically confirmed conditions in their distal fallopian tube(s), 4) with at least 10 patients, and 5) with reports on pregnancy outcomes including the rates of pregnancy, live birth, ectopic pregnancy, and miscarriage. We excluded studies if they were 1) comments or commentary, editorials, letters, communications, 2) about laparotomy, 3) about salpingectomy or hysterectomy, or 4) without reporting on any pregnancy-related outcome.
2.2 Literature search and screening
Literatures were searched from those published on Medline and EMBASE available till to June 1st, 2020. The keywords for searching were “fallopian tube disease” for the diseases and “laparoscopy”, “fimbrioplasty”, and “salpingostomy” for the treatment. Boolean logic “AND” was used to combine the two sets of terms. No limits in language or publication date was set.
Two authors (HH and ZY) independently screened all titles and abstracts and retrieved the full text of any article considered definitely or possibly eligible. Both authors then reviewed the full text articles against the eligibility criteria. Any disagreement between the two authors was resolved by discussion. The reference list of the eligible studies was also screened.
2.3 Data extraction
Data were collaboratively extracted from eligible studies by two investigators (HH and ZY) through a data collection form, which was prior designed to include the first author, the year of publication, the characteristics of the participants including the age, disease histories, disease severities, and the surgeries performed, pregnancy outcomes, and follow-up. We assessed the methodological quality of the included studies using the QUIPS (Quality in Prognostic Studies) tool, which evaluate the methodology in six domains as the study population, the study attrition, the prognostic factor measurement, the outcome measurement, the study confounding, and the statistical analysis. Any disagreements between the two investigators conducting data extraction was firstly resolved through discussion, or by consulting the principal investigator of the study if no consensus could be achieved.
2.4 Statistical analysis
We performed meta-analyses to estimate the pregnancy rate, ectopic pregnancy rate, and miscarriage rate, using the inverse variance method and random effect model. All meta-analyses were conducted through R package metafor [8]. We reported the pooled estimates and their 95% confidence intervals (CI). We conducted subgroup analyses by the surgery types, tubal damage stages, and adhesion. We did not set statistical significance level because no between-group comparison was made.
2.5 Certainty of evidence assessment
We used the GRADE approach (The Grades of Recommendation, Assessment, Development, and Evaluation) to assess the certainty of evidence. The certainty of evidence starts from high and we downgraded the certainty for concerns on risk of bias, inconsistency, indirectness, imprecision, and publication bias.
3 Results
We identified 4039 title and abstract records for screening through systematic search, and 17 records from reference lists. After de-duplicating, 3861 records were finally listed for title and abstract screening. We then retrieved the full texts of 157 studies for further screening and 21 studies concerning 2473 participants were finally included (see Fig. 1. Flow chart). We quantitatively synthesized the results of the 21 included studies. Table 1 summarizes the key characteristics of the eligible studies. Of the 21 studies, 12 studies were from Europe (7 from France, 3 Greece, and 1 each from Germany and Italy), 3 from Asia (2 from China, and 1 from South Korea), 5 from North America (3 from Canada, and 2 from the United States), and 1 from Cameroon. Eleven of the 21 were retrospective analyses, 6 were prospective studies, and 4 did not provide sufficient information. Regarding the types of surgery conducted, patients from 11 studies received salpingostomy. In contrast, 8 studies were on fimbrioplasty and 6 on salpingoneostomy. The median of mean age across the studies was 31, ranging from 28 to 33 years. Of the 21 studies, only 1 study was on women with unilateral tubal pathology, while the study population in 10 studies were women without patent tubes at baseline because either they had bilateral tubal pathology or they had unilateral tubal pathology but the other tube was missing or not operable. Ten other studies did not provide sufficient information on tube patency at baseline. However, only 7 studies were published after year 2000, among them, 3 were published in the last decade.
Key characteristics of included studies.
Flow Diagram for systematic review.
As for the risk of bias, the confounding and statistical analysis of the studies were considered as the two major concerns (Table 2). Most of the included studies only reported the pregnancy outcomes by subgroups, rather than adjusting for confounders using multivariate analyses.
Risk of bias in included studies.
3.1 Pooled estimates
The pooled estimate for the cumulative pregnancy rate of the 2473 participants was 35.1% (95% CI: 30.7%–39.7%, I2 = 78%). The certainty of evidence is low due to serious risk of bias and inconsistency (Fig. 2 and Table 3). We explored the source of heterogeneity across studies by subgroup analysis according to the types of surgery (Fig. 3) and meta-analyses of the pregnancy rates at 1 year and 2 years after surgery (Fig. 4). The pregnancy rates of the patients receiving laparoscopic fimbrioplasty, salpingostomy, salpingoneostomy were 38.0% (95% CI: 32.5%–43.7%, I2 = 0%; 301 patients), 33.6% (95% CI: 28.9%–38.4%, I2 = 43%; 793 patients), and 27.9% (95% CI: 16.7%–40.6%, I2 = 81%; 310 patients), respectively. Heterogeneity exists in subgroups of patients receiving salpingostomy and salpingoneostomy.
Summary of findings for prognosis of patients receiving laparoscopic surgery for distal tubal occlusion.
Meta-analyses of pregnancy rates at different time points after laparoscopic surgeries.
Subgroup analysis of pregnancy rates by types of surgery. F, fimbrioplasty; S, salpingostomy; NS, salpingoneostomy.
Meta-analysis of pregnancy rates after laparoscopic surgeries for distal tubal occlusion.
The rates of the cumulative pregnancy in 1 and 2 year post-surgery were estimated to be 24.8% (95% CI: 13.8%–37.6%, I2 = 95%; 1058 patients) and 33.7% (95% CI: 20.1%–48.7%, I2 = 94%; 823 patients), respectively.
The pooled estimates for the rates of ectopic pregnancies, live births, and miscarriage were 6.2% (95% CI: 4.4%–8.2%, I2 = 61%; 2363 patients; low certainty of evidence due to serious risk of bias and inconsistency), 24.4% (95% CI: 20.2%–28.8%, I2 = 58%; 1154 patients; low certainty due to risk of bias and inconsistency, and 4.6% (95% CI: 2.8%–6.9%, I2 = 10%; 544 patients; low certainty of evidence due to risk of bias and imprecision) (Fig. 5 and Table 3).
Ectopic pregnancy, live birth, and miscarriage after laparoscopic surgeries for distal tubal occlusion.
3.2 Influential factors
We also explored the influential factors of pregnancy prognosis. Of all influential factors, tubal damage stages and adhesion were the mostly reported two factors. Tubal damage stage accounts for the tubal blockage, the quality of the mucosa, and the tubal wall. We adopted scores of 2–5, 6–10, 11–15, >15 to indicate the Stages I, II, III, and IV, respectively. Our analyses indicated that decreasing of the pregnancy rate was associated with the severity of the tubal damages. The pregnancy rates for Stages I, II, III, and IV, were 43.0% (95% CI: 34.7%–51.6%, I2 = 43%; 288 patients), 35.2% (95% CI: 28.5%–42.1%, I2 = 30%; 341 patients), and 14.5% (95% CI: 9.7%–19.9%, I2 = 0%; 248 patients), and 1.3% (95% CI: 0.0%–9.3%, I2 = 64%; 137 patients), respectively (see Fig. 6). Some studies reported the outcomes by tubal damage stages via figures, with no exact numbers of events available. Those studies were not included in our meta-analysis. However, those studies also showed a similar trend with our meta-analysis results. The only study that reported the odds ratios to indicate the association between damaged tubal and pregnancy outcomes were conducted by Audebert et al., who reported that, compared with tubal damage Stage I patients, the odds ratio of delivery for Stage II, Stage III, and Stage IV patients were 0.695 (95% CI: 0.372–1.299), 0.240 (95% CI: 0.112–0.515), and 0.282 (95% CI: 0.108–0.735), respectively. Those odds ratios were based on multivariate analysis, adjusting for age, previous tubal plasty, adhesion, operation technique, and positive Chlamydia testing results. Fig. 7 shows that patients with moderate or severe adhesion had lower pregnancy rates than the patients with mild pelvic adhesion. Audebert et al. also reported a trend showing that severity of tubal adhesion was associated with a lower delivery rate (odds ratio for patients with severe adhesion than patients without adhesion: 0.215, 95% CI: 0.062–0.741) [3].
Pregnancy rates for patients with pelvic adhesion severities.
Pregnancy rates for patients with different tubal damage severities.
Since only one study was on unilateral hydrosalpinx and the majority of the study participants were without patent tubes, we did not conduct subgroup analysis to compare the prognosis of those patients with unilateral versus those with bilateral tubal pathology. Nevertheless, the single study on participants with unilateral hydrosalpinx reported higher probabilities of pregnancy (11 of 23 participants, 47.8%) and intrauterine pregnancy (10 of 23 participants, 43.5%). Table 4 summarizes the results for other influential factors including age, previous hydrosalpinx, other disease or surgery history, i.e., endometriosis. There were only few studies and conflicting results on those factors.
Influential factors studied in the included studies.
3.3 Postoperative reocclusion
We further summarized the evidence on the postoperative reocclusion. There were only three studies that reported patency followed-up after surgery. Because of the variations in following-up time and outcome reporting, we were unable to perform meta-analysis. Oh et al. (1996) reported tubal patency checked via hysterosalpingogram (HSG) in 2 months after operation. Thirteen of 26, 23 of 27, and 28 of 29 patients who respectively received type 1, type 2, and type 3 salpingoneostomy had 1 or both patent tubes patent [9]. In another study, HSG performed on patients in 2 years after surgeries for nonpregnant showed that all the patients with mild disease but no adhesion had both tubes patent, and 80% of the patients with mild disease and adhesions had patent tubes (10). Taylor and colleagues reported that, with a total of 192 tubes undergoing operations, 109 tubes were reassessed postoperatively for nonpregnant patients, 89 of which were patent [5].
4 Discussion
4.1 Summary of findings
With a systematic review and meta-analysis approach, we evaluated the prognosis of the patients underwent laparoscopic surgery treatments for pathology conditions on distal tubal and explored the prognostic factors for pregnancy outcomes for these patients. The cumulative pregnancy rate after laparoscopic surgeries were estimated to be 35.1%. Our estimation represents the prognosis of the patients with pathology conditions on both of the tubes and that of the patients with pathology conditions on the unilateral tube with the other tube missed or inoperable. The results from our estimation are similar to those from another systematic review, which estimated a pregnancy rate of 27% for patients with hydrosalpinx after salpingostomy [11]. The rates for living birth, ectopic pregnancies, and miscarriage were estimated to be 24.4%, 6.2%, and 4.6%, respectively. We further investigated the potential prognostic factors, and found that stage of tubal damages and tubal adhesion were the two that were commonly studied and were associated with worse pregnancy outcomes. However, evidences regarding other prognostic factors are still inconclusive.
Using the GRADE approach [12], we assessed the certainty of evidences in the estimation to the rates of pregnancies, ectopic pregnancies, deliveries, and miscarriages, and concluded that such estimation was based on the studies that were risk of biases concerning confounding and statistical analysis. Confounders accounting for essential bias because the unadjusted reports of pregnancy outcomes make results less comparable across studies. Nevertheless, only two studies undertook multivariate analysis to adjust for confounders. Unexplained heterogeneity, or inconsistency, is another concern. We assessed the certainty of evidence as low for the rates of pregnancies, deliveries, and ectopic pregnancies due to the potential bias and inconsistency. In regarding to the miscarriage rate, the number of events was small, and the estimate was susceptible to random error. Thus, the certainty of evidence for miscarriage rate was also judged to be low due to serious risk of bias and imprecision.
Our subgroup analyses by the surgery types and tubal disease severities also showed a higher pregnancy rates in patients receiving fimbrioplasty than in those receiving salpingostomy and salpingoneostomy [5,13,14]. This may be because the surgery received by a patient represents the indication, or more precisely, the baseline characteristics of the patient [15,16]. This systematic review includes patients with partial and total distal tubal occlusion. Salpingoneostomy is tended to surgically form a new tubal ostium, whereas fimbrioplasty is projected to reconstruct an existent fimbria via desagglutination and dilatation, with serosal incision on a completely occluded tube or a combination of multiple techniques. Our subgroup analysis by baseline tubal disease severity further demonstrated that the degree of pre-surgery tubal damage was associated with the post-surgery decrease of pregnancy rate. It is likely that patients with less severe disease required less complicated surgery, and had better pregnancy outcomes (5). In other words, the observed differences in pregnancy rates after different types of surgery is probably a reflection of baseline disease severity. However, heterogeneity still exists within subgroups of patients receiving salpingostomy and salpingoneostomy, which means that surgery types solely could not explain all the heterogeneity. Notably, inoperable hydrosalpinges, typically characterized by extensive thick-walled, encased, and thick adhesions similar to a frozen pelvis and a worse prognosis, were not considered within the scope of this systematic review.
4.2 Implications for practice
The findings of our systematic review suggest that laparoscopic salpingostomy or fimbrioplasty are alternative strategies for patients with distal tubal pathology, especially for those who are reluctant to receive assisted reproductive treatment. However, multiple factors may have impacts on pregnancy outcomes. We identified several factors including stage of tubal damage and adhesion [3,10,17,18]. Physicians need to discuss with patients about their disease history, uncertainties of evidence, and their expectations. The decision-making process should include consideration to patient preferences, especially for those who have strong preference to preserve fallopian tubes or wish to avoid IVF.
The pregnancy rates at 1 year and 2 years after the surgeries were estimated to be 24.8% and 33.7%, respectively. The estimated rate at 2 years is close to the rate (35.1%) from overall pooled estimate. The studies reporting 2-year post-surgery outcomes suggested that pregnancy would be mostly possible within 2 years after the laparoscopic intervention. Our findings are similar to another review on salpingostomy for hydrosalpinx [11]. With these findings, we suggest that patients who receive surgeries and attempt spontaneous conception should not wait more than 2 years after the surgeries before switching to IVF.
Another concern about surgical correction of the pathological conditions on distal tube is postoperative reocclusion. Our systematic review provided limited evidence on the incidence of postoperative reocclusion. Patients should be informed all alternative strategies preoperatively, because a salpingectomy or proximal tubal occlusion may need to be performed additionally for potential postoperative reocclusion [19].
4.3 Implication for future studies
Prospectively, studies with large size of samples are needed to identify the patients how would mostly benefit from laparoscopic surgeries and the appropriate surgery types for them. Future studies on the incidence of postoperative reocclusion will also contribute to patients’ and physicians’ decisions. Summary of the factors impacting prognosis in our systematic review had laid a foundation for the future research on development of a prediction model for patients with distal tubal pathology.
4.4 Strengths and limitations
This study benefits from the rigorous methods in the breadth of literature search and our assessment of risk of bias and certainty of evidence. We conducted subgroup analyses to compare different time points and types of surgery to explore the heterogeneity. However, potential limitations of the systematic review are the inconsistency and variability across eligibility criteria in the original studies and the variability in study designs, sample sizes, and definitions of the prognostic factors such as tubal disease severity and adhesion. A certain degree of clinical heterogeneity was expected because of the advances of the diagnostic and surgical techniques and the variabilities of the studies in terms of surgeon expertise and technologies across different countries and settings. The included studies also varied in the follow-up time. The short duration means earlier termination of follow-up for patients who had no outcome events occurred, which might underestimate pregnancy outcomes. The purpose for us to conduct meta-analyses on 1 year and 2 years of postoperative pregnancy rates was to mitigate this limitation. Another limitation is that we were unable to estimate the strength of associations between prognostic factors and pregnancy outcomes, other than pooled estimates of pregnancy outcomes for subgroups of patients with different tubal damage and adhesion severities.
5 Conclusion
Low certainty evidence suggested that laparoscopic surgery may restore the tubal function and cure infertility and should be considered as an alternative to IVF. The cumulative pregnancy rate, ectopic pregnancy rate, delivery rate, and miscarriage rate after laparoscopic surgeries were estimated to be 35.1%, 6.2%, 24.4%, and 4.6%. Tubal damage stage and adhesion were associated with worse pregnancy outcomes. The evidence is inconclusive regarding other prognostic factors. These findings will help inform experts in developing a prediction model for patients with distal tubal pathology.
Declaration of competing interest
None.
References
Footnotes
↵1 Hongjing Han and Yuan Zhang contributed equally to this work