Salpingostomy in the treatment of hydrosalpinx: a systematic review and meta-analysis

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Human Reproduction, Vol.0, No.0 pp. 1 14, 2015 doi:10.1093/humrep/dev135 Hum. Reprod. Advance Access published June 16, 2015 REVIEW Infertility Salpingostomy in the treatment of : a systematic review meta-analysis J. Chu 1, H.M. Harb 1, I.D. Gallos 1, R. Dhillon 1, F.M. Al-Rshoud 2, L. Robinson 1, A. Coomarasamy 1, * 1 Academic Department, School of Clinical Experimental Medicine, University of Birmingham, 3rd Floor, Birmingham Women s Hospital Foundation Trust, Metchley Park Road, Edgbaston, Birmingham B15 2TG, UK 2 Medical School, Hashemite University, Az Zarqa, Jordan *Correspondence address. Academic Department, School of Clinical Experimental Medicine, University of Birmingham, 3rd Floor, Birmingham Women s Hospital Foundation Trust, Metchley Park Road, Edgbaston, Birmingham, B15 2TG, UK. Tel: +44-121-623-6835; Fax: +44-121-626-6619; E-mail: a.coomarasamy@bham.ac.uk Submitted on December 22, 2014; resubmitted on May 18, 2015; accepted on May 20, 2015 study question: What is the chance of natural conception when is used to treat?. summaryanswer: The natural clinical pregnancy rate following is 27%, in the hs of experienced surgeons who publish their results. what is known already: Tubal surgery is not commonly offered for women hydrosalpinges since the advent of assisted conception treatment. This is the first systematic review to investigate natural conception rates following in the treatment of. study design, size, duration: A systematic review meta-analysis of 22 observational studies encompasses 2810 patients undergoing attempting natural conception. participants/materials, setting, methods: Literature searches were conducted to retrieve observational studies which reported for. Databases searched included MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials CINAHL, no language restriction. Only studies that focused on (rather than other tubal conserving surgeries) for the treatment of were included. A total of 22 studies matched the inclusion criteria. main results the role of chance: The pooled natural clinical pregnancy rate from the 22 observational studies (including 2810 patients) was 27% (95% confidence interval (CI): 25 29%) after was performed for. The cumulative clinical pregnancy rates were 8.7% (95% CI: 6.6 11.5%) at 6 months, 13.3% (95% CI: 10.6 16.7%) at 9 months, 20.0% (95% CI: 17.5 22.8%) at 12 months, 21.2% (95% CI: 18.6 24.1%) at 18 months 25.5% (95% CI: 22.2 29.4%) at 24 months after. The pooled live birth rate (10 studies, 1469 patients) was 25% (95% CI: 22 28%) after was performed for. The pooled ectopic pregnancy rate (19 studies, 2662 patients) was 10% (95% CI: 9 11%). The pooled miscarriage rate (seven studies, 924 patients) was 7% (95% CI: 6 9%). The included studies scored well on the Newcastle Ottawa quality assessment scale. limitations, reasons for caution: Strict inclusion criteria were used in the conduct of the systematic review. However, the studies included are clinically heterogeneous in many aspects including patient characteristics, surgical technique duration of follow-up after. wider implications of the findings: The findings of this systematic review suggest that is an alternative treatment strategy to tubal clipping or salpingectomy in patients presenting to fertility services. Further prospective, large high quality studies are needed to identify the subpopulation that would most benefit from tube conserving surgery. study funding/competing interest(s): No external funding was either sought or obtained for this study. The authors have no competing interests to declare. trial registration number: N/A. Key words: / / clinical pregnancy / tubal surgery / tubal disease & The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

2 Chu et al. Introduction Approximately 25% of all female fertility is caused by tubal factors (Sharif Coomarasamy 2012). The majority of tubal infertility is caused by ascending infection from sexually transmitted diseases leading to pelvic inflammatory disease (PID) (Bahamondes et al., 1984). If untreated, severe PID can lead to chronic inflammation of the distal Fallopian tubes, which can lead to blockage fluid accumulation known as a. There is substantial evidence that proceeding in vitro fertilization (IVF)/intra-cytoplasmic sprem injection (ICSI) treatment an untreated approximately halves the chances of clinical pregnancy (Andersen et al., 1994; Kassabji et al., 1994; Strell et al., 1994, 1999; Vromme et al., 1995; Akman et al., 1996; Flemming Hull, 1996; Katz et al., 1996; Blazer et al., 1997; Wainer et al., 1997; Freeman et al., 1998; Murray et al., 1998; Van Voorhis et al., 1998; Zeyneloglu et al., 1998; Camus et al., 1999). The exact cause for this has not been fully confirmed but it has been suggested that this may be due to the embryotoxic effect (Kassabji et al., 1994; Savaris Giudice, 2007) or the mechanical washout effect of the fluid (Strell et al., 1994). Before IVF/ICSI treatment became commonplace it was the remit of reproductive surgeons to correct tubal pathology (including ) to enable women to increase their chances of natural conception (Winston Margara, 1991; Winston, 1992; Vromme et al., 1995; Chanelles et al., 2011). These techniques included peritubal adhesiolysis, fimbrioplasty in the most severe tubal disease,. However, since the increased use of IVF/ICSI treatment, is now rarely performed the preference towards sterilizing surgery, such as salpingectomy tubal occlusion, to ensure that hydrosalpingeal fluid is kept separate from the endometrial cavity where the embryo is placed. There is evidence that using these sterilizing techniques doubles the chances of IVF/ICSI success (Strell et al., 1994; Akman et al., 1996; Johnson et al., 2010) in women hydrosalpinges this has now become common clinical practice. The disadvantage of sterilizing surgery is that the patient bilateral disease is then reliant on IVF/ICSI treatment for all future attempts at achieving pregnancy. An alternative management strategy, which conserves a patient s Fallopian tubes, would be to perform followed by a trial of natural conception. If pregnancy is not achieved, women can then be offered IVF treatment or out sterilizing surgery. The aim of our review was to investigate the chances of natural pregnancy after is performed for. Methods Literature search The population of interest consisted of women who for. The primary outcome was natural clinical pregnancy. Secondary outcomes included live birth rates, ectopic pregnancy miscarriage rates. The following electronic databases were searched: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials CINAHL (from inception to March 2015). A search strategy was developed based on the following key words /or medical subject heading (MeSH) terms: tubal surgery, salpingectomy,, in vitro fertilization, intracytoplasmic sperm injection, assisted reproductive techniques,, Fallopian tube disease pregnancy. The reference lists of all primary review articles were examined to identify relevant articles not captured by the electronic searches. No language restrictions were applied in any of the searches or study selection. Study selection Criteria for inclusion in the study were established prior to the literature search. Study selection was carried out by four independent reviewers (J.C., H.M.H., F.M.A. R.D.). First, the titles abstracts of the electronic searches were scrutinized by the independent reviewers. Each title abstract were included or excluded independently according to the predefined inclusion criteria; any disagreements regarding inclusion were resolved by a further reviewer (I.D.G.). The full manuscripts of the titles abstracts that were considered to be relevant for inclusion were obtained. In cases of duplicate publication, the most recent complete versions were selected. Studies that did not explicitly report results from for were excluded. In particular, we excluded studies that were ambiguous their description of surgical treatment did not report specifically on. Data were extracted from full manuscripts by two independent reviewers (J.C. H.M.H.). Validity assessment Two reviewers (J.C. H.M.H.) completed the quality assessment. The Newcastle-Ottawa Quality Assessment Scales for Observational studies were implemented for quality assessment. The quality checklist awards one star as maximum for all items except comparability where a maximum of two stars can be awarded. We used an arbitrary score based on the assumption of equal weight of all items included in the Newcastle-Ottawa Scale. This was used to give a quantitative appraisal of overall quality of the individual studies. The score ranged from 0 to 9, a score of either 0 or 1 for each item. From each study, outcome data were extracted by two reviewers (J.C. H.M.H.). Statistical analysis Clinical pregnancy, ectopic pregnancy, live birth miscarriage rates were extracted from each study. The log of the ratio its corresponding stard error for each study was computed. Meta-analysis using inverse-variance weighting was performed to calculate the rom-effects summary estimates. The square root of this number is the estimated SD of the underlying effects across studies. Because we had relative measures of effect, the confidence intervals (CI) were centred on the natural logarithm of the pooled estimate the limits exponentiated to obtain an interval on the ratio scale. Forest plots were created for each outcome, showing individual study proportions CIs the overall DerSimonian Laird pooled estimate. Heterogeneity of the treatment effects was assessed graphically forest plots statistically analysed using the x 2 -test. Statistical analyses were performed using Stata 12.0 (StataCorp, College Station, TX, USA). Lastly, we performed a stratified analysis splitting studies from 1972 to 1999 from 2000 to 2014 to explore the temporal effects on clinical pregnancy rates. Results The PRISMA flow diagram (Liberati et al., 2009; Moher et al., 2009) of the review process is presented in Fig. 1. The search strategy yielded 14 396 citations of which 14 231 publications were excluded because it was clear from the title or abstract that they did not fulfil the selection criteria. Full manuscripts of 165 articles were obtained. A total of 143 of these publications were excluded because 63 were review articles, opinion letters, case reports or questionnaires; two were duplicate articles; 17 articles

Salpingostomy for 3 Figure 1 Study selection for review on treatment for natural conception. did not specify the nature of the tubal disease 46 performed tubal surgeries other than, e.g. salpingectomy, essure or transvaginal drainage of ; six reported outcomes that were not of interest, e.g. ovarian response after tubal surgery or endometrial receptivity; two articles reported in the IVF population seven articles reported data that could not be extracted. Therefore, the total number of observational studies included in the review was 22. Study characteristics The characteristics of the 22 studies are presented in Table I. Publication dates of the studies varied between 1972 2014. Sample sizes varied from 10 women to 467 women. Of the 22 included studies, 13 reported the ages of their sample populations. Twelve of the studies had a mean age ranged from 27.5 to 32.6. One study had a higher mean age of 35.5. Five studies diagnosed using hysterosalpingogram, four diagnosed using 13 studies using a combination of the two diagnostic modalities. Thirteen of the 22 studies reported results after laparotomy, six reported results after laparoscopic three reported results from mixed surgical techniques. Fourteen of the included studies classified the severity of tubal disease. Two studies reported results after unilateral, five studies reported results after bilateral, while the remaining 15 studies reported on results from a mixture of unilateral bilateral disease. After surgery the length of follow-up of women undergoing varied between 12 71 months. The results of the Newcastle-Ottawa Quality Assessment are presented in Table II. All studies scored well on the Newcastle-Ottawa Quality Assessment Scale, achieving scores between six eight. Clinical pregnancy All 22 studies reported on clinical pregnancy rate as an outcome (Fig. 2). These studies showed a pooled clinical pregnancy rate of 27% (95% CI: 25 29%). There was a substantial level of heterogeneity in these studies indicated by an I 2 value of 53.9%, P ¼ 0.001. Clinical pregnancy rates by publication date The studies were grouped according to their publication date (Fig. 3). Studies published before 2000 had a pooled clinical pregnancy rate of

Table I Study characteristics of included studies. Author (year) Study design Study population Age of study population Method of diagnosis Salpingostomy group Unilateral or bilateral disease Classification of Surgical technique Outcomes (pregnancy rate) Duration of follow-up Cumulative pregnancy data Mean time to conception... Audebert (1980) Audebert et al. (2014) Bayrak et al. (2006) Beyth Bercovici (1982) Boer-Meisel et al. (1986) 172 patients 1976 1979 France 434 patients distal tubal occlusion 1988 2000 France 40 patients hydrosalpinges 1999 2002 USA 31 patients 1976 1979 Israel 108 patients tubal infertility 1974 1981 The Netherls Range 20 40 Range 21 42 Mean age 35.5 + 5.5 Range 21 42 Range 20 43 Mean age 27.5 Range 20 40 Laparoscopy HSG HSG HSG HSG 96 to ampulla, isthmic, type 1 type 2 434 patients everting neo 40 patients cuff Authors noted high age of study population 31 patients 108 patents terminal Bilateral 30/40 (75.0%) Unilateral 10/40 (25.0%) Bilateral 74/108 (68.5%) Unilateral 34/108 (31.5%) By stage of Classified according to mucosal appearances adhesions By size of the, presence of rugae adhesions By size of Classified by size of, thickness of tubal wall condition of endosalpinx Laparotomy IUP 29/96 (30.2%) Laparoscopy IUP 125/434 (28.8%) LBR 106/434 (24.4%) EP 43/434 (9.9%) Laparoscopy 32/40 (80.0%) Laparotomy 8/40 (20.0%) Laparotomy IUP 2/40 (5.0%) EP 1/40 (2.5%) IUP 5/31 (16.1%) Laparotomy IUP 50/108 (46.3%) term pregnancy 24/108 (22.2%) EP 19/108 (17.6%) miscarriage 7/108 (6.5%) 24 months 1 3 month 1/96 (1.0%) 4 6 months 7/96 (7.3%) 7 9 months 14/96 (14.6%) 10 12 months 22/96 (22.9%) 12 23 months 27/96 (28.1%) At 24 months 29/96 (30.2%) 60 months At 3 months IUP 14/432 (3.2%) At 6 months IUP 40/432 (9.3%) At 9 months IUP 58/432 (13.4%) At 12 months IUP 70/432 (3.2%) At 18 months IUP 85/432 (19.7%) At 24 months IUP 101/432 (23.4%) At 36 months IUP 116/432 (26.9%) 22 months At 4 months IUP 1/40 (2.5%) At 7 months IUP 2/40 (5.0%) At 22 months IUP 2/40 (5.0%) 42 months Unable to extract data (only median time of 10.5 cycles reported) 4 Chu et al. Downloaded from http://humrep.oxfordjournals.org/ by guest on June 17, 2015

Bontis Dinas (2000) Chanelles et al. (2011) Chong (1991) Cohen et al. (1972) Dubuisson et al. (1994) to assess a management protocol 258 patients Greece 81 patients managed a tubal surgery protocol 2003 2007 France 34 patients bilateral 1982 1988 USA 706 patients undergoing tubal surgery France 81 infertile women 1986 1991 France Mean age 32.6 +4.7 Not reported HSG or USS 258 patients surgery for 10 patients unilateral Mean age 30.2 HSG 19 patients cuff technique 15 patients Bruhat technique Mean age 30.1 + 4.7 Range 20 39 Not reported HSG 188 patients unilateral : 70 terminal 68 medio-ampullar. 279 patients bilateral : 104 terminal, 122 medio-ampullar. 81 women unilateral or bilateral Unilateral Classified by degree of severity Stages I IV Classified by mucosal tubal stages I IV 39/258 (15.1%) patients 219/258 (84.9%) patients laparotomy Bilateral Laparotomy Bilateral 188/467 (40.3%) Unilateral 279/467 (59.7%) Bilateral 39/81 (48.1%) Unilateral 42/81 (51.9%) IUP 44/258 (17.1%) EP 23/258 (8.9%) 36 months At 36 months IUP 44/258 (17.1%) IUP 3/10 (30%) 12 months At 12 months IUP 3/10 (30%) IUP 9/34 (26.5%) EP 2/34 (5.9%) Laparotomy IUP 89/467 (19.1%) EP 46/467 (9.9%) Classified by severity of disease. Stages I-IV Laparoscopic IUP 26/81 (32.1%) EP 4/81 (4.9%) 2 months No reported 18 months At 18 months IUP 89/467 (19.1%) 24 months IUP cumulative At 12 months 26.4% At 18 months 28.7% At 24 months 29.8% Continued Salpingostomy for 5 Downloaded from http://humrep.oxfordjournals.org/ by guest on June 17, 2015

Table I Continued Author (year) Study design Study population Age of study population Method of diagnosis Salpingostomy group Unilateral or bilateral disease Classification of Surgical technique Outcomes (pregnancy rate) Duration of follow-up Cumulative pregnancy data Mean time to conception... Dubuisson et al. (1995) Jansen (1980) Kosasa Hale (1988) Mage Bruhat (1983) McComb Taylor (2001) Milingos et al. (2000) 123 infertile women 1986 1993 107 patients 1966 1975 Australia 93 patients 1981 1986 Hawaii 68 patients 1977 1981 France 23 patients unilateral a patent contralateral fallopian tube 1988 1997 Canada 61 patients 1990 1997 Greece Mean age 28.5 + 4.9 Range 19 39 All patients,40 Mean age 31 Range 21 39 Range 20 38 Mean age 31.9 Range 25 39 Mean age 31 + 3.9 Range 23 38 HSG Not reported Laparoscopy HSG Laparoscopy HSG 123 laparoscopic 91 patients bilateral 16 patients unilateral 93 patients microsurgical everting 30 patients by electrosurgery 38 patients by CO 2 laser 23 Unilateral laparoscopic 18 salpingostomies sutured, 5 not sutured 61 patients laparoscopic bilateral Bilateral 91/107 (85.0%) Unilateral 16/107 (15.0%) Unilateral 27/93 (29.0%) Bilateral 66/93 (71.0%) Classified by severity of disease. Stages I-IV Laparoscopic IUP 34/123 (30.4%) EP 9/123 (8%) Laparotomy IUP 24/107 (22.4%) Laparotomy Laparotomy Term pregnancy 34/93 (36%) EP 13/93 (14%) 3/93 (3%) Term pregnancy 14/68 (20.6%) EP 6/68 (8.8%) 3/68 (4.4%) Unilateral Laparoscopy IUP rate 10/23 (43.5%) EP rate 1/23 (4%) Bilateral Classified using the AFS scoring system of distal tubal occlusion IUP rate 14/61 (23.0%) EP rate 2/61 (3.3%) Over 24 months Unable to extract IUP cumulative 23.5% at 12 months 26.0% at 15 months 27.7% at 18 months 28.6% at 24 months Unable to extract Unilateral 104 weeks Bilateral 61 weeks 6 At 72 months 10/ 23 (43.5%) 13.4 months 2 Unable to extract 6 Chu et al. Downloaded from http://humrep.oxfordjournals.org/ by guest on June 17, 2015

Singhal et al. (1991) Smalldridge Tait (1993) Taylor et al. (2001) Teoh et al. (1995) Tuli et al. (1984) Winston Margara (1991) 97 patients 1983 1989. UK 30 patients 1986 1990 New Zeal 139 patients 1984 1998 Canada 96 women bilateral hydrosalpinges 1982 1991 Irel 91 women bilateral Canada 388 patients bilateral 1971 1988 UK Mean age 30.4 Range 20 42 Mean age 30.9 + 4.1 Range 21.4 41.1 HSG HSG HSG 97 patients. 30 patients undergoing 139 patients laparoscopic Laparoscopy 96 women bilateral Range 20 37 Mean age 31.5 Range 19 to 44 HSG HSG 23 women CO 2 laser 22 women microdiathermy needle 46 women by cold dissection 323 women primary of unilateral bilateral Classified by size of Laparotomy Laparotomy Unilateral in 86/ 139 Bilateral in 53/ 139 AFS classification system of distal tubal occlusion Laparoscopic Bilateral Laparotomy Bilateral Bilateral Classified by mucosal appearance, thickness of tubal wall peritubal adhesions Modified Boer-Meisel classification. Classified by thickness of tubal wall, appearances of endosalpinx mucosa, tubal adhesions ovarian adhesions IUP, intrauterine pregnancy; EP, ectopic pregnancy; LBR, live birth rate; HSG, hysterosalpingography; USS, ultrasound scan; AFS, American fertility Society. Laparotomy Laparotomy LBR 28/97 (28.9%) IUP 33/97 (34.0%) EP 6/97 (6.2%) 5/97 (5.2%) IUP 9/30 (30.0%) EP 3/30 (10.0%) 0/30 (0.0%) LBR 25/139 (18.0%) IUP 34/139 (24.5%) EP 23/139 (16.5%) 9/139 (6.5%) LBR 19/96 (19.7%) EP 3/96 (3.1%) 1/96 (1.0%) IUP 24/91 (26.4%) EP 6/91 (6.6%) LBR 74/323 (22.9%) IUP 106/323 (32.8%) EP 32/323 (9.9%) 32/323 (9.9%) Mean duration of follow-up 2.8 (range 10 months to 6 ) At12months 28% At36months 40% 9 36 months Unable to extract 36 months Of the patients who conceived: 55.2% in 12 months 84.5% in 36 months 17.7 months (range 0.5 86.4 months) 10 Unable to extract At 5 IUP 24/91 (26.4%) EP 6/91 (6.6%) Variable follow-up duration. Longest 10. 12% of participants lost to follow up reported as not pregnant At 5 IUP 24/91 (26.4%) EP 6/91 (6.6%) At 1 year IUP 55/323 (17.0%) At 4 IUP 106/323 (32.8%) Cumulative rates displayed graphically 23.5 + 4.3 months (range 6 60 months) Salpingostomy for 7 Downloaded from http://humrep.oxfordjournals.org/ by guest on June 17, 2015

Table II Appraisal of methodological quality (Newcastle-Ottawa Scale) of included studies. Study Case- Ascertainment Outcome Comparability by Outcome Duration Adequacy Score representative of exposure negative at start design or analysis assessment of follow-up of follow-up... Audebert (1980) * * * * * * * 7 Audebert et al. (2014) * * * * * * * 7 Bayrak et al. (2006) * * * * * * * 7 Beyth Bercovici (1982) * * * * * x * 6 Boer-Meisel et al. (1986) * * * * * x * 6 Bontis Dinas (2000) * * * * * x * 6 Chanelles et al. (2011) * * * x * * * 6 Chong (1991) * * * * * x * 6 Cohen et al. (1972) * * * x * * * 6 Dubuisson et al. (1995) * * * ** * * * 8 Dubuisson et al. (1994) * * * ** * * * 8 Jansen et al. (1980) * * * x * * * 6 Kosasa Hale (1988) * * * * * x * 6 Mage Bruhat (1983) * * * * * x * 6 McComb Taylor (2001) * * * * * * * 7 Milingos et al. (2000) * * * * * * * 7 Singhal et al. (1991) * * * * * * * 7 Smalldridge Tait (1993) * * * * * * * 7 Taylor et al. (2001) * * * * * * * 7 Teoh et al. (1995) * * * * * x * 6 Tuli et al. (1984) * * * * * * * 7 Winston Margara (1991) * * * * * * * 7 * indicates that a feature is present. X indicates that a feature is absent. However for comparability by design or analysis this checklist awards the maximum of two stars (**), one (*) or none if the feature is completely absent (x). 8 Chu et al. Downloaded from http://humrep.oxfordjournals.org/ by guest on June 17, 2015

Salpingostomy for 9 Figure 2 Natural pregnancy rates after treatment for. 28% (95% CI: 25 30%) studies published after 2000 had a pooled clinical pregnancy rate of 25% (95% CI: 22 29%). Cumulative clinical pregnancy rates Cumulative clinical pregnancy rates over the follow-up period are displayed graphically in Fig. 4. The cumulative clinical pregnancy rates were 8.7% (95% CI: 6.6 11.5%) at 6 months, 13.3% (95% CI: 10.6 16.7%) at 9 months, 20.0% (95% CI: 17.5 22.8%) at 12 months, 21.2% (95% CI: 18.6 24.1%) at 18 months 25.5% (95% CI: 22.2 29.4%) at 24 months. There is a plateau of cumulative clinical pregnancy rate after 24 months. Clinical pregnancy rates in women bilateral hydrosalpinges We analysed the studies that performed in women bilateral hydrosalpinges, as the baseline pregnancy rates (out any surgical treatment) would have been expected to be extremely low in this subpopulation. The pooled clinical pregnancy rate from the five studies of women bilateral hydrosalpinges was 29.0% (95% CI: 25 34%, Fig. 5). There was statistical heterogeneity between these five studies as indicated by an I 2 value of 17.8%, P ¼ 0.301. Live birth Ten studies reported the outcome of live birth (Fig. 6). These studies showed a pooled live birth rate of 25% (95% CI: 22 28%). These studies showed a moderate level of heterogeneity indicated by an I 2 value of 28.8%, P ¼ 0.180. Ectopic pregnancy Nineteen studies reported on the outcome of ectopic pregnancy (Fig. 7). These studies showed a pooled ectopic pregnancy rate of 10% (95% CI: 9 11%). These 19 studies showed a moderate level of heterogeneity indicated by an I 2 value of 41.8%, P ¼ 0.029. Pooling of results from the seven studies that reported on miscarriage as an outcome (Fig. 8) showed a miscarriage rate of 7% (95% CI: 6 9%). There was moderate heterogeneity between these studies an I 2 value of 42.1%, P ¼ 0.110. Discussion This systematic review including 22 studies suggested that in women who undergo for, the chances of achieving a spontaneous pregnancy is 27%. Moreover, the live birth rate for these women is 25%. However, for carries a 10% risk of ectopic pregnancy. Our analysis was strengthened by several factors. We implemented an extensive search strategy a valid data synthesis method. In addition, no language restrictions were applied. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the included studies. The assessment of all studies scored well on this scale, suggesting low risk of bias.

10 Chu et al. Figure 3 Natural pregnancy rates after treatment for by date of publication. Figure 4 Cumulative natural pregnancy rates after treatment for. There is a high degree of clinical heterogeneity of the included studies. Some degree of clinical heterogeneity is to be expected between the studies included in our analysis due to the evolution of the surgical techniques varying approaches to the diagnosis management of hydrosalpinges. However, we do not feel that this is necessarily a disadvantage as heterogeneity can increase the generalisability of the findings. Our studies varied widely regard to the publication dates, the oldest study being published in 1972 the most recent study published in 2014. Techniques used to perform have changed significantly throughout time due to advancements in technology equipment available (Bontis Theodoridis, 2006). Older studies have reported cases where the majority of surgery was performed by laparotomy; newer studies have reported upon cases mainly operated laparoscopically. Although one might expect that the pregnancy rates would be higher in the more recent studies (those published after 2000, which predominately reported laparoscopic as opposed to laparotomy microsurgical techniques), our results suggest that the reverse is true. One possible reason for this is in case selection. Before assisted reproductive treatments were widely available, tubal surgeons may have selected patients milder tubal disease, whom they would expect more favourable outcomes. Furthermore, before 2000 tubal surgery was more popular as a treatment strategy for infertile women. This may have meant that tubal surgeons had greater expertise would have been expected to achieve higher success rates. Another contributing factor is that laparoscopic surgery can take longer to gain competence in therefore it may take several decades to see the change in practice reflected in the pregnancy rates. In theory, laparoscopic surgery should be superior due to a decreased risk of adhesion formation.

Salpingostomy for 11 Figure 5 Natural pregnancy rates after bilateral treatment for bilateral hydrosalpinges. Figure 6 Live birth rates after treatment for. Apart from differences in the expertise of the surgeon, there were differing surgical techniques reported in performing, some using cold dissection others using electrosurgery. Some surgeons performed their salpingostomies an everted edge while others left the edges uneverted. Differing pregnancy outcome may be expected from differing surgical techniques. The age of patient populations undergoing did not vary significantly between the majority of studies. In 12 studies where the

12 Chu et al. Figure 7 Ectopic pregnancy rate after treatment for. Figure 8 rates after treatment for.

Salpingostomy for 13 mean age was reported, the mean age ranged from 27.5 to 32.6. The pooled clinical pregnancy rate of these 12 studies was 31%. One study published by Bayrak et al. (2006) had a higher mean age (35.5 ) had the lowest clinical pregnancy rate (5%). This may suggest that waiting for natural pregnancy are not a suitable management strategy in older women. However, this was a small study of only 40 patients therefore strong conclusions cannot be drawn. Some women in the study population had unilateral disease whilst others had bilateral disease. It may be expected that women unilateral disease have a more favourable outcome. Despite this, clinical pregnancy rates for women bilateral hydrosalpinges treated were still favourable (29% in 605 patients). These studies reporting bilateral showed minimal statistical heterogeneity a low I 2 value, however this must be interpreted care as therewere only five studies, which reduces the power of statistical heterogeneity tests. The size of also differed in study as well as between studies, milder treatment potentially leading to better fertility outcomes. The duration of follow-up of women in the included studies varied widely. Those studies a shorter duration of follow-up may not have reported on women who naturally conceived beyond this time may have therefore under-reported their clinical natural conception rates. The interval between pregnancy is a clinically important factor to consider when counselling women. Women choosing to have tubal conserving surgery in the form of salipingostomy would want to know the duration of time that they should attempt natural conception before considering further treatment. Our data suggest that there is a plateau of cumulative clinical pregnancy rate at 24 months. A Cochrane review published by Johnson et al. (2010) concluded that surgical treatment (salpingectomy or tubal occlusion) should be considered for all infertile women hydrosalpinges prior to IVF treatment. The review did not identify any romized trials to investigate the effectiveness of versus salpingectomy or tubal occlusion prior to IVF treatment. To date there have still been no studies to investigate this. The Cochrane review recommended that further research was required to assess the value of tubal restorative surgery as an alternative (or as a preliminary treatment) to IVF. Our systematic review adds further weight to this recommendation from the Cochrane review, as our results demonstrate that reasonable clinical pregnancy rates can be achieved in carefully selected patients. Salpingostomy may be an important alternative option in selected populations. Women may wish to have the option to have to continue to attempt natural conception before having more definitive sterilizing surgery in the form of salpingectomy, which would lead to a reliance on assisted reproductive treatments no further opportunities to try to conceive naturally. In older women or in women more severe hydrosalpinges it may be more advisable to proceed directly to salpingectomy IVF treatment as time the chances of natural conception are more limited. Summary In the assisted reproduction setting, since the increasing availability of IVF treatment there has been a general trend for the removal or disconnection of fallopian tubes in women who have (Gomel Taylor, 1992). It is likely that the ability of reproductive specialists to restore normal tubal anatomy has been reduced due to an over reliance on tubal removal or disconnection followed by IVF treatment. Importantly, women may not be given the full range of treatment choices in the clinical setting are then left no other option than to pursue fund IVF treatment. The findings of this systematic review have re-introduced the possibility of considering tubal restorative surgery foracarefullyselected group of women. Further research is required to identify the women who would benefit from tube conserving surgery as opposed to the current management of tube removal. It may also be beneficial to investigate the best technique to perform in these selected patients. Acknowledgements We thank Mr Derrick Yates for his assistance in developing the search strategy. We also thank Professor JL Pouly for providing additional data from one of the included studies. Authors Roles J.C., H.M.H. A.C. were responsible for defining the research question. J.C. designed the strategy for the literature search. J.C., H.M.H., F.M.A. R.D. participated in study selection. J.C. H.M.H. performed the quality assessment of included studies. Data extraction was carried out by J.C. H.M.H. Data analysis was performed by I.D.G. J.C., H.M.H. A.C. were the major contributors in manuscript writing. Funding No external funding was either sought or obtained for this study. Conflict of interest None declared. 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