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How to treat hydrosalpinges: IVF as the treatment of choice
RBMOnline - Vol 4. Suppl. 3. 37–39 Reproductive BioMedicine Online; www.rbmonline.com/Article/180 on web 29 October 2001
How to treat hydrosalpinges: IVF as the treatment of choice Annika Strandell Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden Correspondence: Tel: 46–31–342 1000; Fax: 46–31–829248; e-mail: [email protected]
Abstract Two treatment options are available for patients suffering from tubal infertility due to hydrosalpinges. Surgical distal tubal repair is appropriate only for patients with preserved tubal mucosa, otherwise the subsequent intrauterine pregnancy rate is unacceptably low and the ectopic pregnancy rate too high. The alternative treatment, IVF, has also demonstrated low success rate in patients with untreated hydrosalpinges, possibly due to leakage of fluid into the uterus. Salpingectomy has been suggested as a method to overcome the negative influence of the hydrosalpingeal fluid on implantation and embryo development. A randomized controlled trial in Scandinavia has demonstrated a benefit of salpingectomy in patients with hydrosalpinges that were large enough to be visible on ultrasound. If only the first cycle was considered, patients having undergone salpingectomy expressed significantly higher clinical pregnancy (46% versus 22%) and birth (40% versus 17%) rates. It is concluded that patients with large hydrosalpinges and without prospect of spontaneous conception should be recommended salpingectomy, which truly increases their chances of a successful IVF treatment.
Keywords: hydrosalpinges, IVF, salpingectomy, tubal reconstructive surgery
Introduction Infertility caused by hydrosalpinges may be overcome by two different treatment methods. Surgical distal tubal repair was previously performed through laparotomy and microsurgical techniques, which have been replaced by laparoscopy to a large extent today. IVF was introduced as a method of treating tubal factor infertility, and the problems of hydrosalpinges in terms of the risk of ectopic pregnancy were discussed in the first publication on clinical IVF pregnancy (Steptoe and Edwards, 1976). Today, patients with hydrosalpinges have been identified as a subgroup with significantly impaired pregnancy outcome compared with patients suffering from other types of tubal damage. One of the main explanations implies that the leakage of hydrosalpingeal fluid into the uterine cavity creates an unfavourable endometrial environment for implantation and could also affect embryo development. According to this theory, any surgical intervention interrupting communication to the uterus would remove the leakage of the hydrosalpingeal fluid and restore pregnancy rates. The combination of salpingectomy, which is the only surgical method that has been evaluated in a randomized controlled trial, and subsequent IVF will be discussed as a main method to treat patients with hydrosalpinges.
Background Retrospective studies have indicated that the larger the hydrosalpinx, the worse the outcome after IVF, which raises the question of embryotoxic properties of the fluid. However, the results of embryo cultures in hydrosalpingeal fluid have been contradictory among murine models (Mukherjee et al., 1996; Murray et al., 1997), and studies of human embryo development did not express any toxic influence of
hydrosalpingeal fluid (Strandell et al., 1998). The lack of substrate in pure hydrosalpingeal fluid is harmful to embryo development, but the potential embryotoxic property of hydrosalpingeal fluid is still a controversy. It has also been suggested that the leakage of fluid to the uterine cavity, causing a watery interface, is enough to prevent implantation. Whatever the exact mechanism, an interruption of the communicating hydrosalpinx seems appropriate to improve the endometrial environment for implantation.
Salpingectomy Hitherto, salpingectomy has been the only method of prophylactic surgery in patients with hydrosalpinx that has been properly evaluated in a randomized controlled trial (Strandell et al., 1999). The surgical procedure was performed laparoscopically by using mono- or bipolar diathermy and scissors on the proximal tube and the mesosalpinx to excise the hydrosalpinx. The multicentre study in Scandinavia showed a significant improvement in pregnancy and birth rates after salpingectomy in patients with hydrosalpinges that were large enough to be visible on ultrasound before ovarian stimulation was initiated when the first cycle was considered. Clinical pregnancy rates were 46% versus 22% (P = 0.049) and birth rates were 40% versus 17% (P = 0.040) in salpingectomized patients versus patients without any surgical intervention (Table 1). Patients were offered up to three stimulated cycles, and those who were randomized to undergo salpingectomy achieved a cumulative birth rate of 55%. When all subsequent cycles were considered, including all patients regardless of the size of the hydrosalpinx, salpingectomy implied a doubled birth rate compared with patients with persistent hydrosalpinges. Data revealed that the benefit of salpingectomy mainly affected patients with hydrosalpinges visible on ultrasound; consequently, those are the only patients
37
IVF treatment of hydrosalpinges - A Strandell
Table 1. Implantation and pregnancy rates in the first transfer cycle in a subgroup of patients with bilateral and/or ultrasound visible hydrosalpinges at inclusion, in the two treatment groups of salpingectomy or no intervention prior to IVF. P-value (Fisher’s exact test)
Treatment group
Ultrasound visible (n) Implantation rate n/n (%) Clinical pregnancy rate n (%) Ongoing or delivery rate n (%) Bilateral and ultrasound visible (n) Implantation rate n/n (%) Clinical pregnancy rate n (%) Ongoing or delivery rate n (%)
Laparoscopic salpingectomy
No intervention before IVF
35 21/70 (30.0) 16 (45.7)
40 13/78 (16.7) 9 (22.5)
14 (40.0)
20 16/39 (41.0) 12 (60.0) 11 (55.0)
to be recommended prophylactic salpingectomy prior to IVF. The psychological aspect of removing the tubes in an infertile patient is very important and has to be considered. Even if it is obvious that the patient would benefit from salpingectomy, it is crucial that she is psychologically prepared to undergo the procedure. In some cases it takes one or several failed cycles before the patient is ready to give her consent. Salpingectomy of a unilateral hydrosalpinx may even imply an increased chance of spontaneous conception, illustrated by two women in the Scandinavian study who conceived spontaneously and achieved a full-term pregnancy.
Salpingectomy versus functional surgery
38
Is there a risk of unnecessary salpingectomies being performed when a clear recommendation of salpingectomy has been formulated to a defined patient group? Only patients with preserved mucosa within their hydrosalpinges have a fair pregnancy chance (50–64%) subsequent to reconstructive surgery, but they are also at an increased risk of having an ectopic pregnancy (Dubuisson et al., 1994, Marana et al., 1999). Even within this good prognosis group, approximately half the patients will be considered for IVF after failure to achieve a full-term pregnancy. Unnecessary salpingectomies should not be performed and may be avoided easily by appropriate evaluation of the tubal mucosa at laparoscopy before any final decision of salpingectomy is made. It is important that physicians discriminate carefully whether a hydrosalpinx should be removed or is suitable for surgical repair.
7 (17.5)
19 4/37 (10.8) 3 (15.8) 3 (15.8)
0.077 0.049 0.040
0.004 0.008 0.019
Salpingectomy versus less invasive surgery Is tubal ligation as effective as salpingectomy? There are no results from randomized trials to answer this question. The data from two retrospective studies have not shown any significant differences in pregnancy outcome, but the number of patients has been too low to allow for any conclusion (Stadtmauer et al., 2000; Surrey and Schoolcraft, 2001). In one of the retrospective studies, 45 of 60 patients with hydrosalpinges accepted laparoscopic surgery, and salpingectomy was performed where possible, while tubal ligation and distal drainage was performed in cases of extensive adhesions (Stadtmauer et al., 2000). Only the surgically untreated group expressed significantly lower clinical pregnancy rates. The least invasive surgical method, transvaginal ultrasoundguided aspiration of fluid, has been described in several case reports and in two retrospective studies. Different conclusions regarding the benefit of drainage at the time of oocyte retrieval in terms of improved pregnancy and implantation rates were drawn (Sowter et al., 1997; Van Voorhis et al., 1998). The first and largest study showed no effect on pregnancy rates, while the latter study showed a significant improvement. There is a rapid reoccurrence of fluid already noticeable at the time of transfer in many cases, which is likely to compromise any beneficial effect of drainage. There is a need to evaluate transvaginal aspiration properly at the time of oocyte retrieval, including the potential risk of infection associated with the puncture of a hydrosalpinx. The occurrence of infections in association with puncture of a hydrosalpinx seems to be rare when antibiotics have been given, according to the published
IVF treatment of hydrosalpinges - A Strandell
reports. The method has the advantage of being less invasive than the other available surgical methods. Today, there is no evidence that transvaginal aspiration is as effective as salpingectomy, but for patients who will not undergo salpingectomy, and for those who develop tubal fluid during stimulation, it is an option.
Surgical versus medical treatment The use of antibiotics has also been discussed, not only as a prophylactic when a hydrosalpinx has been punctured but also when given to selected groups of patients with elevated serum Chlamydia trachomatis immunoglobulin G (IgG) antibody titres or as a routine before oocyte retrieval for all patients (Sharara et al., 1996). However, antibiotic treatment specifically in hydrosalpinx patients has never been prospectively evaluated. One retrospective study has compared patients with hydrosalpinx who received extended doxycyclin treatment during an IVF cycle to patients with other indications (tubal occlusion without hydrosalpinx/adhesions or endometriosis/unexplained infertility) who did not receive antibiotics (Hurst et al., 2001). Implantation and pregnancy rates were similar in all groups, suggesting that antibiotic treatment would minimize the detrimental effect of hydrosalpinx. The method is cheap and simple, but its benefit still needs to be evaluated in a prospective trial.
Conclusion Hydrosalpinges with destroyed mucosa are not suitable for reconstructive surgery. However, patients with these also have an impaired success rate after IVF, possibly due to the leakage of fluid into the uterus. Salpingectomy is the only method that has been properly evaluated as a surgical approach to overcome the negative influence of the hydrosalpingeal fluid. From the Scandinavian study a clear conclusion was drawn: patients with hydrosalpinges large enough to be visible on ultrasound examination can be recommended laparoscopic salpingectomy prior to IVF in order to enhance their chance of a full-term pregnancy. Patients with large hydrosalpinges and without prospect of spontaneous conception should be recommended a salpingectomy, which truly increases their chances of a successful IVF treatment.
References Dubuisson JB, Chapron C, Morice P et al. 1994 Laparoscopic salpingostomy: fertility results according to the mucosal appearance. Human Reproduction 9, 334–339. Hurst BS, Tucker KE, Awoniyi CA, Schlaff WD 2001 Hydrosalpinx treated with extended doxycyclin does not compromise the success of in vitro fertilization. Fertility and Sterility 75, 1017–1019. Marana R, Catalano GF, Muzii M et al. 1999 The prognostic role of salpingoscopy in laparoscopic tubal surgery. Human Reproduction 14, 2991–2995. Mukherjee T, Copperman AB, McCaffrey C et al. 1996 Hydrosalpinx fluid has embryotoxic effects on murine embryogenesis: a case for prophylactic salpingectomy. Fertility and Sterility 66, 851–853. Murray CA, Clarke HJ, Tulandi T, Tan SL 1997 Inhibitory effect of human hydrosalpingeal fluid on mouse preimplantation embryonic development is significantly reduced by the addition of lactate. Human Reproduction 12, 2504–2507. Sharara FI, Scott Jr RT, Marut EL et al. 1996 In-vitro fertilization outcome in women with hydrosalpinx. Human Reproduction 11, 526–530. Sowter MC, Akande VA, Williams JA et al. 1997 Is the outcome of in-vitro fertilization and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx? Human Reproduction 12, 2147–2150. Stadtmauer LA, Riehl RM, Toma SK et al. 2000 Cauterization of hydrosalpinges before in vitro fertilization is an effective surgical treatment associated with improved pregnancy rates. American Journal Obstetrics and Gynecology 183, 367–371. Steptoe PC, Edwards RG 1976 Reimplantation of a human embryo with subsequent tubal pregnancy. The Lancet 1, 880–882. Strandell A, Sjögren A, Bentin-Ley U et al. 1998 Hydrosalpinx fluid does not adversely affect the normal development of human embryos and implantation in vitro. Human Reproduction 13, 2921–2925. Strandell A, Lindhard A, Waldenström U et al. 1999 Hydrosalpinx and IVF outcome: A prospective, randomized multicentre trial in Scandinavia on salpingectomy prior to IVF. Human Reproduction 14, 2762–2769. Surrey ES, Schoolcraft WB 2001 Laparoscopic management of hydrosalpinges before in vitro fertilization-embryo transfer: salpingectomy versus proximal tubal occlusion. Fertility and Sterility 75, 612–617. Van Voorhis BJ, Sparks AE, Syrop CH et al. 1998 Ultrasound-guided aspiration of hydrosalpinges is associated with improved pregnancy and implantation rates after in-vitro fertilization cycles. Human Reproduction 13, 736–739.
39
How to treat hydrosalpinges: IVF as the treatment of choice Annika Strandell Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden Correspondence: Tel: 46–31–342 1000; Fax: 46–31–829248; e-mail: [email protected]
Abstract Two treatment options are available for patients suffering from tubal infertility due to hydrosalpinges. Surgical distal tubal repair is appropriate only for patients with preserved tubal mucosa, otherwise the subsequent intrauterine pregnancy rate is unacceptably low and the ectopic pregnancy rate too high. The alternative treatment, IVF, has also demonstrated low success rate in patients with untreated hydrosalpinges, possibly due to leakage of fluid into the uterus. Salpingectomy has been suggested as a method to overcome the negative influence of the hydrosalpingeal fluid on implantation and embryo development. A randomized controlled trial in Scandinavia has demonstrated a benefit of salpingectomy in patients with hydrosalpinges that were large enough to be visible on ultrasound. If only the first cycle was considered, patients having undergone salpingectomy expressed significantly higher clinical pregnancy (46% versus 22%) and birth (40% versus 17%) rates. It is concluded that patients with large hydrosalpinges and without prospect of spontaneous conception should be recommended salpingectomy, which truly increases their chances of a successful IVF treatment.
Keywords: hydrosalpinges, IVF, salpingectomy, tubal reconstructive surgery
Introduction Infertility caused by hydrosalpinges may be overcome by two different treatment methods. Surgical distal tubal repair was previously performed through laparotomy and microsurgical techniques, which have been replaced by laparoscopy to a large extent today. IVF was introduced as a method of treating tubal factor infertility, and the problems of hydrosalpinges in terms of the risk of ectopic pregnancy were discussed in the first publication on clinical IVF pregnancy (Steptoe and Edwards, 1976). Today, patients with hydrosalpinges have been identified as a subgroup with significantly impaired pregnancy outcome compared with patients suffering from other types of tubal damage. One of the main explanations implies that the leakage of hydrosalpingeal fluid into the uterine cavity creates an unfavourable endometrial environment for implantation and could also affect embryo development. According to this theory, any surgical intervention interrupting communication to the uterus would remove the leakage of the hydrosalpingeal fluid and restore pregnancy rates. The combination of salpingectomy, which is the only surgical method that has been evaluated in a randomized controlled trial, and subsequent IVF will be discussed as a main method to treat patients with hydrosalpinges.
Background Retrospective studies have indicated that the larger the hydrosalpinx, the worse the outcome after IVF, which raises the question of embryotoxic properties of the fluid. However, the results of embryo cultures in hydrosalpingeal fluid have been contradictory among murine models (Mukherjee et al., 1996; Murray et al., 1997), and studies of human embryo development did not express any toxic influence of
hydrosalpingeal fluid (Strandell et al., 1998). The lack of substrate in pure hydrosalpingeal fluid is harmful to embryo development, but the potential embryotoxic property of hydrosalpingeal fluid is still a controversy. It has also been suggested that the leakage of fluid to the uterine cavity, causing a watery interface, is enough to prevent implantation. Whatever the exact mechanism, an interruption of the communicating hydrosalpinx seems appropriate to improve the endometrial environment for implantation.
Salpingectomy Hitherto, salpingectomy has been the only method of prophylactic surgery in patients with hydrosalpinx that has been properly evaluated in a randomized controlled trial (Strandell et al., 1999). The surgical procedure was performed laparoscopically by using mono- or bipolar diathermy and scissors on the proximal tube and the mesosalpinx to excise the hydrosalpinx. The multicentre study in Scandinavia showed a significant improvement in pregnancy and birth rates after salpingectomy in patients with hydrosalpinges that were large enough to be visible on ultrasound before ovarian stimulation was initiated when the first cycle was considered. Clinical pregnancy rates were 46% versus 22% (P = 0.049) and birth rates were 40% versus 17% (P = 0.040) in salpingectomized patients versus patients without any surgical intervention (Table 1). Patients were offered up to three stimulated cycles, and those who were randomized to undergo salpingectomy achieved a cumulative birth rate of 55%. When all subsequent cycles were considered, including all patients regardless of the size of the hydrosalpinx, salpingectomy implied a doubled birth rate compared with patients with persistent hydrosalpinges. Data revealed that the benefit of salpingectomy mainly affected patients with hydrosalpinges visible on ultrasound; consequently, those are the only patients
37
IVF treatment of hydrosalpinges - A Strandell
Table 1. Implantation and pregnancy rates in the first transfer cycle in a subgroup of patients with bilateral and/or ultrasound visible hydrosalpinges at inclusion, in the two treatment groups of salpingectomy or no intervention prior to IVF. P-value (Fisher’s exact test)
Treatment group
Ultrasound visible (n) Implantation rate n/n (%) Clinical pregnancy rate n (%) Ongoing or delivery rate n (%) Bilateral and ultrasound visible (n) Implantation rate n/n (%) Clinical pregnancy rate n (%) Ongoing or delivery rate n (%)
Laparoscopic salpingectomy
No intervention before IVF
35 21/70 (30.0) 16 (45.7)
40 13/78 (16.7) 9 (22.5)
14 (40.0)
20 16/39 (41.0) 12 (60.0) 11 (55.0)
to be recommended prophylactic salpingectomy prior to IVF. The psychological aspect of removing the tubes in an infertile patient is very important and has to be considered. Even if it is obvious that the patient would benefit from salpingectomy, it is crucial that she is psychologically prepared to undergo the procedure. In some cases it takes one or several failed cycles before the patient is ready to give her consent. Salpingectomy of a unilateral hydrosalpinx may even imply an increased chance of spontaneous conception, illustrated by two women in the Scandinavian study who conceived spontaneously and achieved a full-term pregnancy.
Salpingectomy versus functional surgery
38
Is there a risk of unnecessary salpingectomies being performed when a clear recommendation of salpingectomy has been formulated to a defined patient group? Only patients with preserved mucosa within their hydrosalpinges have a fair pregnancy chance (50–64%) subsequent to reconstructive surgery, but they are also at an increased risk of having an ectopic pregnancy (Dubuisson et al., 1994, Marana et al., 1999). Even within this good prognosis group, approximately half the patients will be considered for IVF after failure to achieve a full-term pregnancy. Unnecessary salpingectomies should not be performed and may be avoided easily by appropriate evaluation of the tubal mucosa at laparoscopy before any final decision of salpingectomy is made. It is important that physicians discriminate carefully whether a hydrosalpinx should be removed or is suitable for surgical repair.
7 (17.5)
19 4/37 (10.8) 3 (15.8) 3 (15.8)
0.077 0.049 0.040
0.004 0.008 0.019
Salpingectomy versus less invasive surgery Is tubal ligation as effective as salpingectomy? There are no results from randomized trials to answer this question. The data from two retrospective studies have not shown any significant differences in pregnancy outcome, but the number of patients has been too low to allow for any conclusion (Stadtmauer et al., 2000; Surrey and Schoolcraft, 2001). In one of the retrospective studies, 45 of 60 patients with hydrosalpinges accepted laparoscopic surgery, and salpingectomy was performed where possible, while tubal ligation and distal drainage was performed in cases of extensive adhesions (Stadtmauer et al., 2000). Only the surgically untreated group expressed significantly lower clinical pregnancy rates. The least invasive surgical method, transvaginal ultrasoundguided aspiration of fluid, has been described in several case reports and in two retrospective studies. Different conclusions regarding the benefit of drainage at the time of oocyte retrieval in terms of improved pregnancy and implantation rates were drawn (Sowter et al., 1997; Van Voorhis et al., 1998). The first and largest study showed no effect on pregnancy rates, while the latter study showed a significant improvement. There is a rapid reoccurrence of fluid already noticeable at the time of transfer in many cases, which is likely to compromise any beneficial effect of drainage. There is a need to evaluate transvaginal aspiration properly at the time of oocyte retrieval, including the potential risk of infection associated with the puncture of a hydrosalpinx. The occurrence of infections in association with puncture of a hydrosalpinx seems to be rare when antibiotics have been given, according to the published
IVF treatment of hydrosalpinges - A Strandell
reports. The method has the advantage of being less invasive than the other available surgical methods. Today, there is no evidence that transvaginal aspiration is as effective as salpingectomy, but for patients who will not undergo salpingectomy, and for those who develop tubal fluid during stimulation, it is an option.
Surgical versus medical treatment The use of antibiotics has also been discussed, not only as a prophylactic when a hydrosalpinx has been punctured but also when given to selected groups of patients with elevated serum Chlamydia trachomatis immunoglobulin G (IgG) antibody titres or as a routine before oocyte retrieval for all patients (Sharara et al., 1996). However, antibiotic treatment specifically in hydrosalpinx patients has never been prospectively evaluated. One retrospective study has compared patients with hydrosalpinx who received extended doxycyclin treatment during an IVF cycle to patients with other indications (tubal occlusion without hydrosalpinx/adhesions or endometriosis/unexplained infertility) who did not receive antibiotics (Hurst et al., 2001). Implantation and pregnancy rates were similar in all groups, suggesting that antibiotic treatment would minimize the detrimental effect of hydrosalpinx. The method is cheap and simple, but its benefit still needs to be evaluated in a prospective trial.
Conclusion Hydrosalpinges with destroyed mucosa are not suitable for reconstructive surgery. However, patients with these also have an impaired success rate after IVF, possibly due to the leakage of fluid into the uterus. Salpingectomy is the only method that has been properly evaluated as a surgical approach to overcome the negative influence of the hydrosalpingeal fluid. From the Scandinavian study a clear conclusion was drawn: patients with hydrosalpinges large enough to be visible on ultrasound examination can be recommended laparoscopic salpingectomy prior to IVF in order to enhance their chance of a full-term pregnancy. Patients with large hydrosalpinges and without prospect of spontaneous conception should be recommended a salpingectomy, which truly increases their chances of a successful IVF treatment.
References Dubuisson JB, Chapron C, Morice P et al. 1994 Laparoscopic salpingostomy: fertility results according to the mucosal appearance. Human Reproduction 9, 334–339. Hurst BS, Tucker KE, Awoniyi CA, Schlaff WD 2001 Hydrosalpinx treated with extended doxycyclin does not compromise the success of in vitro fertilization. Fertility and Sterility 75, 1017–1019. Marana R, Catalano GF, Muzii M et al. 1999 The prognostic role of salpingoscopy in laparoscopic tubal surgery. Human Reproduction 14, 2991–2995. Mukherjee T, Copperman AB, McCaffrey C et al. 1996 Hydrosalpinx fluid has embryotoxic effects on murine embryogenesis: a case for prophylactic salpingectomy. Fertility and Sterility 66, 851–853. Murray CA, Clarke HJ, Tulandi T, Tan SL 1997 Inhibitory effect of human hydrosalpingeal fluid on mouse preimplantation embryonic development is significantly reduced by the addition of lactate. Human Reproduction 12, 2504–2507. Sharara FI, Scott Jr RT, Marut EL et al. 1996 In-vitro fertilization outcome in women with hydrosalpinx. Human Reproduction 11, 526–530. Sowter MC, Akande VA, Williams JA et al. 1997 Is the outcome of in-vitro fertilization and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx? Human Reproduction 12, 2147–2150. Stadtmauer LA, Riehl RM, Toma SK et al. 2000 Cauterization of hydrosalpinges before in vitro fertilization is an effective surgical treatment associated with improved pregnancy rates. American Journal Obstetrics and Gynecology 183, 367–371. Steptoe PC, Edwards RG 1976 Reimplantation of a human embryo with subsequent tubal pregnancy. The Lancet 1, 880–882. Strandell A, Sjögren A, Bentin-Ley U et al. 1998 Hydrosalpinx fluid does not adversely affect the normal development of human embryos and implantation in vitro. Human Reproduction 13, 2921–2925. Strandell A, Lindhard A, Waldenström U et al. 1999 Hydrosalpinx and IVF outcome: A prospective, randomized multicentre trial in Scandinavia on salpingectomy prior to IVF. Human Reproduction 14, 2762–2769. Surrey ES, Schoolcraft WB 2001 Laparoscopic management of hydrosalpinges before in vitro fertilization-embryo transfer: salpingectomy versus proximal tubal occlusion. Fertility and Sterility 75, 612–617. Van Voorhis BJ, Sparks AE, Syrop CH et al. 1998 Ultrasound-guided aspiration of hydrosalpinges is associated with improved pregnancy and implantation rates after in-vitro fertilization cycles. Human Reproduction 13, 736–739.
39