Surgical treatment for tubal disease in women due to undergo in vitro fertilisation (Unknown)

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1 Surgical treatment for tubal disease in women due to undergo in vitro fertilisation (Unknown) Johnson NP, Mak W, Sowter MC This is a reprint of a Cochrane unknown, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2001, Issue 3

2 T A B L E O F C O N T E N T S HEADER ABSTRACT PLAIN LANGUAGE SUMMARY BACKGROUND OBJECTIVES RESULTS DISCUSSION ACKNOWLEDGEMENTS REFERENCES SOURCES OF SUPPORT i

3 [Intervention Unknown] Surgical treatment for tubal disease in women due to undergo in vitro fertilisation NP Johnson 1, W Mak, MC Sowter 1 Obstetrics & Gynaecology Department, National Women s Hospital, Auckland, NEW ZEALAND Contact address: Editorial group: Cochrane Menstrual Disorders and Subfertility Group. Publication status and date: Unchanged, published in Issue 2, Citation: Johnson NP, Mak W, Sowter MC. Surgical treatment for tubal disease in women due to undergo in vitro fertilisation. The Cochrane Database of Systematic Reviews, Issue. Art. No.: CD DOI: / CD Background A B S T R A C T Tubal disease, and particularly hydrosalpinx, has a detrimental effect on the outcome of in-vitro fertilisation (IVF). It has been less clear whether surgical intervention for tubal disease prior to IVF is effective in improving the likelihood of successful outcome. Most data are retrospective or poorly controlled. To date no single prospective randomised trial has shown a significant benefit from such surgical treatment prior to IVF. Objectives To assess the value of surgical treatment for tubal disease prior to IVF. Search strategy The search strategy of the Menstrual Disorders and Subfertility Group was used for the identification of relevant randomised controlled trials. Selection criteria All trials where a surgical treatment for tubal disease was compared with a control group generated by randomisation were considered for inclusion in the review. Data collection and analysis Three randomised controlled trials were identified and included in this review, after an attempt to obtain further information from the authors of all three trials. All trials were assessed for quality criteria. The studied outcomes were live birth (and ongoing pregnancy), pregnancy, ectopic pregnancy, miscarriage, multiple pregnancy, complications, implantation rate and the proportion of IVF cycles resulting in embryo transfer. Main results The odds of pregnancy (OR 1.75, 95%CI 1.07, 2.86) and of ongoing pregnancy and live birth (OR 2.13, 95%CI 1.24, 3.65) were increased with laparoscopic salpingectomy for hydrosalpinges prior to IVF. There was no significant difference in the odds of ectopic pregnancy (OR 0.42, 95%CI 0.08, 2.14), miscarriage (OR 0.49, 95%CI 0.16, 1.52), treatment complications (OR 5.80, 95%CI 0.35, 96.79) or implantation rate (OR 1.34, 95%CI 0.87, 2.05). No data were available concerning the odds of multiple pregnancy or the proportion of IVF cycles resulting in embryo transfer. 1

4 Reviewers conclusions Laparoscopic salpingectomy should be considered for all women with hydrosalpinges prior to IVF treatment. Currently unilateral salpingectomy for a unilateral hydrosalpinx (bilateral salpingectomy for bilateral hydrosalpinges) should be recommended, although this requires further evaluation. Further randomised trials are required to assess other surgical treatments for hydrosalpinx, such as salpingostomy, tubal occlusion or needle drainage of a hydrosalpinx at oocyte retrieval. The role of surgery for tubal disease in the absence of a hydrosalpinx is unclear and merits further evaluation. P L A I N L A N G U A G E S U M M A R Y Synopsis Removing blocked or diseased fallopian tubes before IVF can increase pregnancy rates for women on the IVF program. Diseases such as hydrosalpinx (watery substances in blocked fallopian tubes) can severely reduce the chances of pregnancy while on the IVF program because of damage to the fallopian tubes. A salpingectomy (removing the damaged fallopian tube) can be done to remove the blocked part of the tube. The review of trials found laparoscopic salpingectomy prior to IVF treatment increases the odds of pregnancy and live birth. However, the procedure is very delicate. More research is needed to examine this and other treatments. B A C K G R O U N D A spectrum of severity of tubal disease is recognised at laparoscopy from peritubal adhesions, through damaged fimbriae or distorted tubal anatomy, tubal blockage, to hydrosalpinx (a fluid-filled distension of the fallopian tube in the presence of distal tubal occlusion - a severe manifestation of tubal disease). In-vitro fertilisation (IVF) was first developed as a fertility treatment to overcome mechanical obstruction for women without functional fallopian tubes (Steptoe 1978). Recently it has been recognised that tubal pathology is associated with a low embryo implantation rate in IVF compared to the other causes of infertility (Englert 1987; Strandell 1994; Andersen 1994; Fleming 1996). The presence of a hydrosalpinx may also be associated with increased risk for early pregnancy loss (Strandell 1994). The failure of IVF in women with tubal disease may be related to the severity of tubal damage (Csemiczky 1996; Vasquez 1995). One theory to explain the deleterious effect of a hydrosalpinx on the outcome of IVF is the intermittent bathing of the intrauterine environment with toxic fluid within the hydrosalpinx. The fluid contains bacteriological agents, debris, lymphocytes, cytokines, lymphokines and prostaglandins. Hydrosalpinx fluid may reduce the receptive capabilities of the endometrium (Strandell 1994; Fleming 1996; Katz 1996; Freeman 1996; Akman 1996) possibly by reducing endometrial expression of beta-integrin (Meyer 1997). It may have direct embryo toxicity (Mukherjee 1996) and may also exert a negative influence on oocytes in early follicular recruitment (Freeman 1996). Studies using historical control groups have suggested that the outcome of IVF may be improved by surgical treatment of hydrosalpinges (Meyer 1997; Poe-Ziegler 1995; Vandromme 1995; Shelton 1996; Puttemans 1996; Andersen 1996). This would need to be confirmed by a robust prospective randomised controlled trial. It is also uncertain whether unilateral or bilateral salpingectomy would be necessary to obtain benefit in the case of unilateral hydrosalpinx; whether less invasive surgical interventions could be beneficial, for example occluding the fallopian tube with a hydrosalpinx immediately adjacent to the uterus (thereby preventing uterine spillage of potentially harmful hydrosalpinx fluid), salpingoplasty (where the surgery would allow continuous drainage rather than accumulation of hydrosalpinx fluid) or needle aspiration of hydrosalpinx fluid (which could be performed under ultrasound guidance at the time of IVF egg collection). Not all studies have demonstrated a negative effect of hydrosalpinx on IVF outcome (Shahara 1996). Many clinicians have been so convinced by the published studies to date that they routinely perform, for example, salpingectomy in women with hydrosalpinges prior to IVF. Such surgery, whether performed at laparotomy or laparoscopy, is not without risk to the woman. For women who have suffered from infertility to the extent that IVF is the planned treatment, it is often a major decision to undergo a surgical procedure which removes any possibility of conceiving spontaneously. Many gynaecologists are aware of women who were deemed to 2

5 have hopeless tubal infertility who have later conceived spontaneously. It is therefore important to have the best available evidence that these interventions are beneficial. O B J E C T I V E S To assess the value of surgical treatment of tubal disease prior to IVF. The following surgical treatments for tubal disease were considered: salpingectomy (both unilateral and bilateral), tubal occlusion (both unilateral and bilateral), salpingoplasty and hydrosalpinx fluid aspiration. The hypothesis that surgical treatment of tubal disease prior to IVF is beneficial by increasing the pregnancy and live birth rate, without substantially increasing complications related to the intervention, was tested. R E S U L T S Meta-analysis of randomised trials Surgical treatment for hydrosalpinges versus non-surgical management significantly increased the odds of live birth plus ongoing viable pregnancy (OR 2.13, 95%CI 1.24, 3.65), and of pregnancy (OR 1.75, 95%CI 1.07, 2.86). No significant differences were seen in the odds of ectopic pregnancy (OR 0.42, 95%CI 0.08, 2.14), miscarriage per pregnancy (OR 0.49, 95%CI 0.16, 1.52), treatment complications (OR 5.80, 95%CI 0.35, 96.79) or implantation per embryo transferred (OR 1.34, 95%CI 0.87, 2.05). There were no data available concerning the odds of multiple pregnancy or the proportion of IVF stimulation cycles resulting in embryo transfer. The chi-square results for heterogeneity across trials were not significant for any of the interventions for which data was available. If the Goldstein 1998 trial results were excluded from the metaanalysis, the results were not qualitatively altered. Meta-analysis of results based only on the Dechaud 1998 and Strandell 1999 trials gave the following odds ratios: Live birth plus ongoing pregnancy 1.99 (95%CI 1.13, 3.51) Pregnancy 1.73 (95%CI 1.03, 2.91) Ectopic pregnancy 0.53 (95%CI 0.09, 3.13) Miscarriage per pregnancy 0.55 (95%CI 0.16, 1.92) Treatment complications 5.86 (95%CI 0.35, 96.79) Implantation per embryo transferred 1.34 (95%CI 0.87, 2.05) Non-randomised trials The results non-randomised trials where the control group did not include women (or couples) acting as their own controls, are included in the other tables section (Non-randomised Comparative Studies) for descriptive purposes only, but have not been included in the meta-analysis. The results of non-randomised trials must be interpreted cautiously. Two trials concluded a significant increase in the odds of pregnancy from aspiration of hydrosalpinges at the time of egg collection (Savic 1999; Vandromme 1995); one concluded no significant increase in the odds of pregnancy from this intervention (Sowter 1997); one found no significant increase in the odds of pregnancy from aspiration of hydrosalpinges prior to the IVF stimulation cycle (Aboulghar 1990); one found significantly fewer pregnancies in women who did not undergo hydrosalpinx surgery compared to those who underwent laparoscopic salpingectomy or proximal tubal cautery (Stadtmauer 2000). D I S C U S S I O N Claims have been made by several authors during the last ten years that the likelihood of successful IVF treatment in women with hydrosalpinges can be increased by prior salpingectomy. In many studies, this conclusion was based on non-randomised data and therefore prone to bias. This led to a shift in clinical practice in favour of surgical treatment of hydrosalpinges prior to IVF. Recent insightful publications have highlighted the fact that, whilst it was clear that women with hydrosalpinges had a reduced likelihood of success from IVF, a statistically significant benefit of the surgical treatment of hydrosalpinges had not been demonstrated in randomised trials (Dechaud 2000; Puttemans 2000). Our metaanalysis of randomised trials does show a statistically significant benefit of laparoscopic salpingectomy for hydrosalpinges prior to IVF. A number needed to treat calculation suggests that between 7 and 8 women (95% confidence interval 2-25; control live birth rate of 16%) would need to have a salpingectomy prior to IVF to gain one additional live birth. Injudicious conclusions can lead to inappropriate intervention. Laparoscopic salpingectomy, particularly in the context of hydrosalpinx or tubal disease where the fallopian tube may have severe adhesions, is by no means without hazard and should be undertaken only by adequately trained laparoscopic surgeons. Operative laparoscopy carries a small risk of major visceral or vascular injury. A further concern is whether salpingectomy could adversely affect ovarian egg reserve - salpingectomy dissection must be performed very close to the fallopian tube to avoid disrupting the ovarian blood supply. Lass 1999 suggested proximal clamping and distal fenestration of the fallopian tube to avoid the problem of disruption of blood supply, an approach used in the Strandell 1999 trial if extensive adhesions were present. The intervention can therefore only be justified in the context of clear benefit in terms of the successful outcome of IVF, namely the delivery of a healthy baby. Many of the non-randomised studies used historical controls, where the women who underwent surgical treatment for their tubal disease acted as their own controls by considering their IVF cycles prior to the surgical intervention. This is clearly flawed. 3

6 With a technique such as IVF where success rates have typically improved substantially within a period of a few years, those cycles performed more recently would be expected to have a higher chance of success. Worse still, in many of the studies, the selection for salpingectomy was based on previous IVF failure, yet the data from these failed cycles was still considered within the control group (Mardesic 1999; Poe-Ziegler 1995; Shelton 1996; Vandromme 1995). Randomisation is the only method to minimise these types of bias. The three randomised trials in this review were pooled for the meta-analysis. None of the trials demonstrated statistical significance in there own right. However pooling their data for metaanalysis demonstrated an increased chance of pregnancy and live birth or ongoing pregnancy in women undergoing surgical treatment for hydrosalpinges prior to IVF versus those receiving no surgical treatment. Was it appropriate to pool the data from these trials, given that the interventions assessed were subtly different in each case? All three trials involved women with at least one hydrosalpinx. Two trials involved the intervention salpingectomy - Dechaud 1998 employed routine bilateral salpingectomy, Strandell 1999 employed uni- or bi-lateral salpingectomy depending on whether the hydrosalpinx was uni- or bi-lateral; one trial involved salpingostomy and selective proximal salpingectomy in those women with proximal tubal blockage (Goldstein 1998). The control group interventions were also subtly different in each trial, but all involved a non-surgical approach to hydrosalpinges. In essence, all three trials compared a group who underwent laparoscopic surgery on a fallopian tube to prevent hydrosalpinx fluid spill into the uterine cavity versus a group who did not have this surgical intervention. There was no statistical heterogeneity for any outcomes across trials, supporting the decision to pool the data. The Goldstein 1998 trial differed from the other two trials as follows: (a) it was the only trial not fully published in a peer-reviewed medical journal; (b) it included only couples with previous failed IVF and had a very low pregnancy rate in the control group; (c) it compared surgical versus medical treatment. If this trial had not been included in the meta-analysis, pooling of the data from the two trials of surgical treatment versus no intervention produced conclusions which did not differ qualitatively for any outcomes, compared to the meta-analysis of all three trials. The meta-analysis failed to show a significant effect on the odds of miscarriage. Andersen 1994 and Zeyneloglu 1998 suggested that pregnancy loss was more common in women with hydrosalpinges. Shahara 1996 did not show that pregnancy loss was more common in women with hydrosalpinges. There was also no significant effect on the odds of ectopic pregnancy, although there was a total of only 5 ectopic pregnancies occurring in the entire trial populations, a surprisingly low number in this high-risk group (Johnson 1998). Whilst it is rational to expect a reduction in the likelihood of ectopic pregnancy following salpingectomy for a hydrosalpinx, this meta-analysis was underpowered to demonstrate a significant difference in the odds of ectopic pregnancy. What intervention? Laparoscopic salpingectomy proved to be the only surgical intervention for which substantive data were available for this review (with a small contribution from laparoscopic selective salpingostomy-salpingectomy in the Goldstein 1998 trial. It is incumbent upon those who promote surgical interventions other than salpingectomy to demonstrate in a randomised trial that the results are as good as for salpingectomy. (a) Transvaginal needle aspiration of a hydrosalpinx under ultrasound guidance (either before an IVF stimulation cycle or at the time of oocyte retrieval) is the least invasive intervention. Nonrandomised trials (Non-randomised Comparative Studies) have conflicted in their conclusions as to the effectiveness of this intervention. However rapid reaccumulation of fluid, demonstrated by Bloeche 1997 to recur within 3 days of hydrosalpinx aspiration at oocyte retrieval, could compromise the success of this intervention. (b) Proximal tubal occlusion, by a Filschie clip or electrosurgical cauterisation, might be expected to prevent uterine spill of hydrosalpinx contents. No prospective randomised data is available to support this approach. (c) Those promoting restorative surgery for the fallopian tube (which should prevent hydrosalpinx fluid accumulation) on the grounds that there may be a few spontaneous pregnancies within this group, also need to produce data that the intervention has equivalent effectiveness to laparoscopic salpingectomy preceding IVF. Andersen 1996 argues that approximately one third of women with hydrosalpinges have a good prognosis for spontaneous pregnancy after reconstructive surgery. However the expertise required to select this population (including assessment by salpingoscopy) is not available to most women. Puttemans 1996 has suggested that salpingostomy should be the first choice surgical intervention if the hydrosalpinx is thin-walled and free from ampullary adhesions. There is a risk of ectopic pregnancy with such an approach and this outcome should be considered in any trial comparing salpingectomy prior to IVF versus restorative surgery. Laparoscopic salpingectomy followed by IVF is not the only treatment option for women with hydrosalpinges, since there is an argument in favour of IVF and restorative tubal surgery being used as complementary treatment strategies for tubal disease (Gillett 1997). This review did not examine the issue of tubal surgery versus IVF for tubal infertility. Should routine bilateral salpingectomy be performed for hydrosalpinx whether or not bilateral hydrosalpinges are present (the approach of Dechaud 1998)? There is no evidence from this review that the routine bilateral salpingectomy approach is superior - to the contrary, the results of Strandell 1999, in adopting an approach 4

7 of removing only fallopian tubes affected by a hydrosalpinx, are at least as good as those of Dechaud It is rational to adopt the less invasive approach of Strandell There are cases where unilateral salpingectomy for a hydrosalpinx in the context of lengthy tubal infertility has resulted in spontaneous pregnancy soon after the surgery (Choe 1999). Should surgical treatment be performed before the first cycle or only after previous unsuccessful IVF treatment owing to embryo non-implantation? The pooled data from Dechaud 1998 and Strandell 1999, both of whom included only women who had not previously undergone IVF, confirm that salpingectomy prior to IVF is an effective intervention for women undergoing their first IVF cycle. Should diseased fallopian tubes in the absence of hydrosalpinx be treated surgically prior to IVF? The theoretical rationale is that salpingectomy for blocked fallopian tubes or those with such severe disease that they are deemed non-functional, may reduce the likelihood of ectopic pregnancy. Additionally a hydrosalpinx may be an intermittent phenomenon and salpingectomy for a diseased tube removes the possibility that it will develop into a hydrosalpinx. There is currently no data to support this approach. Subgroup analysis for the 39 women with bilateral hydrosalpinges visible on ultrasound (Strandell 1999) suggested that this subgroup had the greatest effect from salpingectomy prior to IVF, which was associated with a 2.4-fold increase in the delivery rate, a result which reached statistical significance in its own right within the trial (p=0.019). This finding must be interpreted with caution since it is unclear whether this was a pre-specified subgroup analysis, although it suggests that it may be women with the most severe tubal disease who benefit most from laparoscopic salpingectomy. A C K N O W L E D G E M E N T S The authors acknowledge the helpful comments of those who have refereed this review and the authors of included trials who supplied additional information or data. We wish to thank Sarah Hetrick, the Review Group Coordinator, for attentive assistance and Sue Furness, Trials Search Coordinator, for assistance with identification of trials. R E F E R E N C E S References to studies included in this review Dechaud 1998 {published data only} Dechaud H, Daures JP, Amal F, Humeau C, Hedon B. Does previous salpingectomy improve implantation and pregnancy rates in patients with severe tubal factor infertility who are undergoing in vitro fertilization? A pilot prospective randomized study. Fertility & Sterility 1998;69: Dechaud H, Daures JP, Arnal F, Humeau C, Hedon B. Salpingectomy before undergoing IVF can increase implantation rates in severe tubal infertility patients: a prospective randomised study. Human Reproduction Abstracts of 13th Annual Meeting of the ESHRE. 1997;12: Goldstein 1998 {published data only} Goldstein DB, Sasaran LH, Stadtmauer L, Popa R. Selective salpingostomy-salpingectomy (SSS) and medical treatment prior to IVF in patients with hydrosalpinx. Fertility & Sterility (Abstracts of 1998 Meetings). 1998;70 (3, Suppl 1)(3):S320. Strandell 1999 {published data only} Strandell A, Lindhard A, Waldenstrom U, Thorburn J, Janson PO, Hamberger L. Hydrosalpinx and IVF outcome: a prospective randomized multicentre trial in Scandinavia on salpingectomy prior to IVF. Human Reproduction 1999; 14(11): References to studies excluded from this review Mardesic 1999 Mardesic T, Muller P, Voboril J, Hulvert J, Huttelova R, Becvarova V, Mikova M. The influence of salpingectomy of hydrosalpinges visible on ultrasound on IVF results. A pilot prospective randomized study. Abstracts of 11th World Congress on In Vitro Fertilization and Human Reproductive Genetics. Sydney, Australia: 9-14 May, 1999: 156. References to studies awaiting assessment Masson 1999 Additional references Aboulghar 1990 Aboulghar MA, Mansour RT, Serour GI, Sattar MA, Awad MM, Amin Y. Transvaginal ultrasonic needle guided aspiration of pelvic inflammatory masses before ovulation induction for in vitro fertilization. Fertil Steril 1990;53:311. Akman 1996 Akman MA, Garcia JE, Damewood MD, Watts LD, Katz E. Hydrosalpinx affects the implantation of previously cryopreserved embryos. Hum Reprod 1996;11: Andersen 1994 Andersen A, Yue Z, Meng F, Petersen K. Low implantation rate after in-vitro fertilisation in patients with hydrosalpinges diagnosed by ultrasonography. Hum Reprod 1994;9:

8 Andersen 1996 Andersen AN, Lindhard A, Loft A, Ziebe S, Andersen CY. The infertile patient with hydrosalpinges: IVF with or without salpingectomy?. Hum Reprod 1996;11: Bloeche 1997 Bloeche M, Schreiner Th, Lisse K. Recurrence of hydrosalpinges after transvaginal aspiration of tubal fluid in an IVF cycle with development of a serometra. Hum Reprod 1997;12: Choe 1999 Choe J, Check JH. Salpingectomy for unilateral hydrosalpinx may improve in vivo fecundity. Gynecol Obstet Invest 1999;48: Csemiczky 1996 Csemiczky G, Landgren BM, Fried G, Wramsby H. High tubal damage grade is associated with low pregnancy rate in women undergoing in vitro fertilisation treatment. Hum Reprod 1996;11: Dechaud 2000 Dechaud H, Hedon B. What effect dues hydrosalpix have on assisted reproduction? The role of salpingectomy remains contraversial. Hum Reprod 2000;15: Englert 1987 Englert Y, Vekemans M, Lejeune B, Van Rysselberge M, Puissant F, Degueldre M, Leroy F. Higher pregnancy rates after in vitro fertilization and embryo transfer in cases with sperm defects. Fertil Steril 1987;48: Fleming 1996 Fleming C, Hull MGR. Impaired implantation after in vitro fertilisation treatment associated with hydrosalpinx. Br J Obstet Gynaecol 1996;103: Freeman 1996 Freeman MR, Whitworth CM, Hill GA. Hydrosalpinx reduces in vitro fertilisation / embryo transfer rates and in vitro blastocyst development. 52nd Annual Meeting of the American Fertility Society. 1996:S211. Gillett 1997 Gillett WR. Evaluation of long term outcome following tubal microsurgery. Ass Reprod Reviews 1997;8: Johnson 1998 Johnson N, McComb P, Gudex G. Heterotopic pregnancy complicating in vitro fertilisation. Aust N Z J Obstet Gynaecol 1998;38: Katz 1996 Katz E, Akman MA, Damewood MD, Garcia JE. Deleterious effect of the presence of hydrosalpinx on implantation and pregnancy rates with in vitro fertilisation. Fertil Steril 1996;66: Meyer 1997 Meyer WR, Castelbaum AJ, Somkuti S, Sagoskin AW, Doyle M, Harris JE, Lessey BA. Hydrosalpinges adversely affect markers of endometrial receptivity. Hum Reprod 1997;12: Mukherjee 1996 Mukherjee T, Copperman AB, McCaffrey C, Cook CA, Bustillo M, Obasaju MF. Hydrosalpinx fluid has direct embryotoxic effects on murine embryogenesis: a case for prophylactic salpingectomy. Fertil Steril 1996;66: Poe-Ziegler 1995 Poe-Ziegler R, Shelton KE, Toner JP. Salpingectomy(ies) improves the pregnancy rate after IVF in patients with unilateral or bilateral hydrosalpinx. J Assist Reprod Genet 1995;12:S65. Puttemans 1996 Puttemans PJ, Brosens IA. Salpingectomy improves in vitro fertilisation outcome in patients with a hydrosalpinx: blind victimisation of the fallopian tube?. Hum Reprod 1996;11: Puttemans 2000 Puttemans P, Campo R, Gordts S, Brosens I. Hydrosalpinx - functional surgery or salpingectomy?. Hum Reprod 2000; 15: Savic 1999 Savic B, Milacic D, Peako N. Hydrosalpingeal fluid aspiration during oocyte retrieval has beneficial effect on outcome of in-vitro fertilization-embryo transfer. Abstracts of the 15th Annual Meeting of the ESHRE. 1999:310. Shahara 1996 Shahara FI, Scott RT Jr, Marut EL, Queenan JT Jr. In-vitro fertilisation outcome in women with hydrosalpinx. Hum Reprod 1996;11: Shelton 1996 Shelton KE, Butier L, Toner JP. Salpingectomy improves the pregnancy rate in in vitro fertilisation patients with hydrosalpinx. Hum Reprod 1996;11: Sowter 1997 Sowter MC, Akande VA, Williams JA, Hull MG. Is the outcome of in-vitro fertilisation and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx?. Hum Reprod 1997;12: Stadtmauer 2000 Stadtmauer LA, Riehl RM, Toma SK, Talbert LM. Cauterization of hydrosalpinges before in vitro fertilization is an effective surgical treatment associated with improved pregnancy rates. Am J Obstet Gynecol 2000;183: Steptoe 1978 Steptoe PC, Edwards RG. Birth after the reimplantation of a human embryo. Lancet 1978;2:366. Strandell 1994 Strandell A, Waldenstrom U, Nilsson L, Hamberger L. Hydrosalpinx reduces in-vitro fertilisation / embryo transfer pregnancy rates. Hum Reprod 1994;9: Van Voorhis 1998 Van Voorhis BJ, Sparks AET, Syrop CH, Stovall DW. Ultrasound-guided aspiration of hydrosalpinges is associated with improved pregnancy and implantation rates after in-vitro fertilization cycles. Hum Reprod 1998;13:

9 Vandromme 1995 Vandromme J, Chasse E, Lejeune B, Van Rysselberge M, Delvigne A, Leroy F. Hydrosalpinges in in vitro fertilisation: an unfavourable prognostic feature. Hum Reprod 1995;10: Vasquez 1995 Vasquez G, Boeckx K, Brosens IA. Prospective study of tubal mucosal lesions and fertility in hydrosalpinges. Hum Reprod 1995;10: Zeyneloglu 1998 Zeyneloglu HB, Arici A, Olive DL. Adverse effects of hydrosalpinx on pregnancy rates after in vitro fertilization - embryo transfer. Fertil Steril 1998;70: Indicates the major publication for the study S O U R C E S O F S U P P O R T External sources of support No sources of support supplied Internal sources of support University of Auckland, School of Medicine, Auckland NEW ZEALAND 7

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