Study characteristics

Methods

Parallel RCT

Participants

Country: China

Site: Center for Reproductive Medicine, Gansu Provincial Hospital of Maternity and Children Healthcare, Lanzhou, China.

Participants: 229 women with recently diagnosed hydrosalpinx by either HSG or laparoscopy prior to undergoing IVF‐ET, of which Group A (94 women) underwent transvaginal aspiration of hydrosalpinx and auricular point sticking (a form of acupuncture); Group B (89 women) underwent transvaginal aspiration of hydrosalpinx only; and Group C (46 women) underwent no intervention.

Mean age: range 20 to 40 years.

Inclusion: women with hydrosalpinx diagnosed by contrast imaging or laparoscopy, aged 20 to 40 years, wishing to conceive.

Exclusion: patients with any of the following ‐ acute pelvic infection; high blood pressure; endocrine disease (e.g. diabetes, hyperthyroidism, hyperprolactinaemia, Stein‐Leventhal syndrome); endometriosis; and adenomyosis.

IVF protocol: A daily injection of GnRH agonist at a dose of 3.75 mg i.m. was administered from day 2 of the menstrual cycle. On day 7 of the cycle, a transvaginal ultrasound was performed to measure endometrial thickness. Following 30 days of GnRH agonist injections, 2 mg estradiol valerate was administered p.o. once daily for four days and increased by 1 mg at a time until endometrial thickness reached 8 to 10 mm. No details were provided regarding oocyte collection, embryo transfer or luteal phase support.

Interventions

Group A underwent transvaginal aspiration of hydrosalpinx and auricular point sticking; Group B underwent transvaginal aspiration of hydrosalpinx only; and Group C received no intervention.

No further details of the interventions are provided.

Outcomes

1. Clinical pregnancy rate (as confirmed by ultrasound at 35 days) per woman randomised (n/n)

2. Multiple pregnancy rate (n/n)

3. Early miscarriage rate (not defined) (n/n)

4. Ectopic pregnancy rate (not defined) (n/n)

Notes

We did not obtain responses after emailing the authors to obtain clarification and further details of their methodology and outcomes.

The authors did not specify a trial registration number.

It is unclear whether power calculation was undertaken.

There is no mention of any funding sources involved in the study.

It is unclear whether an intention‐to‐treat analysis was performed.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Random digit table"

Allocation concealment (selection bias)

Unclear risk

Not specified.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

No blinding performed.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not specified.

Incomplete outcome data (attrition bias)
Intention to treat for primary outcome?

High risk

Out of 229 women randomised, only 217 were analysed. No explanation was given for the 12 participants whose data were not analysed.

Selective reporting (reporting bias)

Unclear risk

Not specified.

Other bias

Unclear risk

Apart from stating that participants' age and duration of infertility did not differ across all groups, no further mention is made regarding differences in demographic characteristics.

Study characteristics

Methods

Parallel RCT

Participants

Country: France

Site: Single centre ‐ Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire Arnaud de Villeneuve, Montpellier, France.

Participants: 60 women with severe tubal infertility diagnosed by either HSG or laparoscopic surgery, not suitable for tubal repair, were included (30 underwent laparoscopic salpingectomy, and 30 did not receive any treatment prior to undergoing IVF).

Mean age ± SD: 30.6 ± 3.3 (control group) and 31.7 ± 4.5 (salpingectomy group).

Inclusion: women with severe tubal infertility, not suitable for tubal repair, with all other fertility investigations normal. HSG criteria for severe tubal disease included extensive inflammatory disease in the proximal part of the tube with diverticula extending to > 2 cm of the isthmus (salpingitis isthmica nodosa) or a hydrosalpinx with poor prognosis due to abnormal mucosal folds or irregular walls. Laparoscopic criteria for severe tubal pathology included the presence of proximal nodes or an inflamed and thick‐walled hydrosalpinx. Adhesions alone were considered insufficient to make a diagnosis of severe tubal pathology.

Exclusion: patients older than 40 years; additional causes of infertility; tubal pathology suitable for repair by tubal catheterization, laparoscopic surgery or microsurgical techniques; severe tubal pathology requiring bilateral salpingectomy as part of treatment; lack of patient consent for salpingectomy or randomisation.

IVF protocol: All participants underwent pituitary desensitization with GnRH agonist (Decapeptyl LP 3.75 mg i.m.; Ipsen, Paris, France) starting on day 1 or 2 of the menstrual cycle and administered once daily for 14 days. Pituitary desensitization was assessed at the end of the 14 days of GnRH agonist injections by ultrasound (no follicles measuring > 10 mm in diameter) and serum estradiol levels (< 60 pg/mL). All women then received a 7‐day course of i.m. injections of hMG (Humegon; Organon, Paris, France) at a dose of 300 IU once daily and an additional injection of 150 IU once daily. The dose of hMG was adjusted according to daily ultrasound monitoring of follicle development and serum estradiol levels. Once an estradiol level above 1500 pg/mL and at least three follicles measuring more than 17 mm in diameter were identified, hCG at a dose of 5000 IU i.m. was administered. Oocyte retrieval occurred under ultrasound guidance 35 hours after hCG administration.

Embryo transfer took place 48 hours after oocyte retrieval in all women for whom embryos were obtained after IVF. The number of embryos transferred was determined according to the age of the participant, the level of ovarian response, the fecundity of the oocytes, embryo morphology and counselling of the couple.

Interventions

All included women underwent laparoscopy. On the day before surgery, informed consent for potential bilateral salpingectomy was obtained from all participants. At the time of laparoscopy, those with a surgical diagnosis of tubal disease not suitable for repair were randomised to undergo either adhesiolysis and bilateral salpingectomy OR adhesiolysis only.

Outcomes

1. Implantation rate (number of implanted embryos divided by the number of fresh embryos replaced into the uterine cavity) (n/n, %)

2. Number of oocytes retrieved per cycle (mean ± SD)

3. Number of embryos obtained per cycle (mean ± SD)

4. Pregnancy rate ‐ not defined; reported per transfer, per oocyte retrieval and per IVF cycle (n/n, %)

5. Ongoing pregnancy rate ‐ not defined (n/total transfers, %)

6. Ectopic pregnancy and miscarriage rate ‐ not defined (n/n, %)

Notes

For the purposes of meta‐analysis, the review authors used the ongoing pregnancy rate as clinical pregnancy rate.

The authors did not specify a trial registration number.

A power calculation was performed but not adhered to as the number calculated (322 participants in each group) could not be achieved in the trial setting.

No statement regarding competing interests.

Presence or absence of funding is not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"the patients were assigned randomly either to undergo bilateral salpingectomy or not to undergo salpingectomy"

Allocation concealment (selection bias)

Unclear risk

Not specified.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not specified.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not specified.

Incomplete outcome data (attrition bias)
Intention to treat for primary outcome?

Low risk

Intention to treat analysis is unclear, however the number randomised is the same as the number analysed. No statement regarding loss to follow‐up or withdrawals.

Selective reporting (reporting bias)

Low risk

No suggestion of selective reporting.

Other bias

Low risk

There were no significant differences in participant characteristics.

Study characteristics

Methods

Parallel RCT

Participants

Country: The Netherlands

Site: Two‐centre study performed in one academic hospital (VU University Medical Centre, Amsterdam, the Netherlands) and one teaching hospital (Spaarne Gasthuis, Hoofddorp, the Netherlands).

Participants: 85 women with unilateral or bilateral hydrosalpinges visible at ultrasound and confirmed with HSG or at laparoscopy who were scheduled for an IVF/ICSI treatment, of which 42 were allocated to hysteroscopic proximal tubal occlusion by intratubal device placement (Essure®) and 43 were allocated to laparoscopic salpingectomy prior to ART.

Mean age ± SD: 32.6 ± 4.5 years (Essure®) and 32.0 ± 4.5 years (Laparoscopic salpingectomy).

Inclusion: Women aged 18 to 41 years old with a diagnosis of unilateral or bilateral hydrosalpinx (defined as a distally occluded Fallopian tube which became pathologically dilated during tubal patency testing) confirmed by HSG or at laparoscopy prior to undergoing ART.

Exclusion: pelvic inflammatory disease within the previous 6 months; hydrosalpinges with evidence of proximal blockage; women in whom laparoscopic salpingectomy was precluded by a frozen pelvis diagnosed at a previous laparoscopy; women with type 0 or 1 fibroids interfering with Essure® insertion; and refusal to undergo Essure® insertion.

IVF protocol: All participants underwent IVF/ICSI 12 weeks after treatment of hydrosalpinges. GnRH agonists or antagonists were used to achieve pituitary down‐regulation. Further details of the local IVF protocol are not provided. The authors analysed the first IVF/ICSI cycle (including fresh and all frozen‐thawed embryo transfers) following the treatment of hydrosalpinges.

Interventions

Participants were randomised to undergo either hysteroscopic proximal tubal occlusion with Essure® intratubal devices OR laparoscopic salpingectomy.

Hysteroscopic proximal tubal occlusion with Essure® intratubal devices: all Essure® devices (Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA) were inserted in an outpatient setting with antibiotic prophylaxis (Doxycycline 200 mg for 5 days). A rigid hysteroscope (5.5 mm with 5‐Fr working channel, Olympus Netherlands B.V.) was used and the Essure® micro‐inserts were placed in the proximal end of the Fallopian tube (unilateral or bilateral according to the presence of hydrosalpinx). A maximum of three coils were allowed to protrude into the uterine cavity. A follow‐up HSG was performed 12 weeks after Essure® to confirm proximal occlusion of the hydrosalpinges.

Laparoscopic salpingectomy: depending on whether one or two hydrosalpinges were present, a unilateral or bilateral salpingectomy was performed. In those diagnosed with extensive pelvic adhesions at laparoscopy precluding salpingectomy, proximal tubal ligation using a two‐site isthmic diathermy technique was performed as an alternative to salpingectomy. Conversion to laparotomy was not allowed. All participants who underwent laparoscopy received perioperative antibiotic prophylaxis with cefuroxime 1500 mg i.v. and metronidazole 500 mg i.v.

Outcomes

1. Units of gonadotrophins (median, IQR)

2. Number of retrieved oocytes (median, IQR)

3. Number of embryos (mean ± SD)

4. Implantation rate (defined as the number of gestational sacs on ultrasound divided by the number of embryos transferred) (n/n, %)

5. Ongoing pregnancy per woman randomised (defined as the presence of a fetal heartbeat on ultrasound beyond 10 weeks of pregnancy following one IVF/ICSI cycle) (n/n, %)

6. Miscarriage rate per woman randomised (n/n, %)

7. Ectopic pregnancy rate per woman randomised (n/n, %)

8. Live birth rate per woman randomised (n/n, %)

9. Proximal tubal occlusion rate after Essure® placement

10. Differences in ovarian reserve before and 3 months after treatment of hydrosalpinges (variable units)

11. Time to ongoing pregnancy (months)

12. Infection rate following intervention per woman randomised (n/n, %)

Notes

Further data on participant characteristics (specifically with regards to the severity of male factor infertility in eligible participants) and outcomes were obtained through written correspondence with the authors.

The study was prospectively registered on the Dutch Trial Register (NTR 2073).

A power calculation was performed but not followed. The calculated sample size required a total of 426 participants per group, which the authors did not consider feasible. Instead, only women with hydrosalpinges large enough to be visible on ultrasound were included.

One author received 'non‐financial support from Conceptus Inc'.

The Essure® device has been withdrawn by the manufacturer since publication of Dreyer 2016 and is no longer available.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"computer‐generated randomization list with block sizes of four"

Allocation concealment (selection bias)

Low risk

"independent data manager"

Blinding of participants and personnel (performance bias)
All outcomes

High risk

"The study was unblinded"

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not specified.

Incomplete outcome data (attrition bias)
Intention to treat for primary outcome?

Low risk

"Women who were randomised, but never started IVF/ICSI treatment were included for the ITT analyses". Loss to follow‐up was accounted for according to patient allocation: 2 women allocated to Essure® were lost to follow‐up; and another 2 allocated to salpingectomy were lost to follow‐up.

Selective reporting (reporting bias)

Low risk

No suggestion of selective reporting.

Other bias

Low risk

There were no differences in baseline characteristics between the two groups.

Study characteristics

Methods

Parallel RCT

Participants

Country: Egypt

Site: Single centre ‐ Assisted conception unit of Ahmed Elgazzar hospital, Cairo, Egypt.

Participants: 110 women with unilateral or bilateral hydrosalpinges diagnosed by ultrasound, of which 55 patients underwent ultrasound‐guided aspiration of hydrosalpinx prior to IVF‐ET (Group A) and 55 women received no intervention prior to IVF‐ET (Group B).

Mean age ± SD: 28.16 ± 3.62 (Group A) and 29.38 ± 4.03 (Group B).

Inclusion: women aged 18‐37 years with unilateral or bilateral hydrosalpinges visible by ultrasound; body mass index 19‐29 kg/m²; infertility lasting longer than 1 year; normal basal LH, FSH and prolactin concentrations; and normal semen analysis.

Exclusion: patients with uterine fibroids requiring surgical removal; endometriosis; male‐factor infertility requiring ICSI; previous IVF cycles; history of recurrent miscarriage; known endocrinologic disorders; and the presence of systemic disease contraindicating pregnancy.

IVF protocol: All included women underwent IVF with a long GnRH agonist protocol using Leuprorelin acetate (Lucrin, Abbott, Australasia) at a daily dose of 1 mg s.c., starting 1 week before the anticipated date of the next menstrual period (usually day 21 of the cycle preceding the IVF‐ET cycle). Once pituitary downregulation was achieved (ultrasound confirming the absence of cysts in the ovaries and endometrial thickness < 5 mm; and serum estradiol < 50 pg/mL), the dose of Leuprorelin acetate was halved and controlled ovarian stimulation was commenced. Where pituitary downregulation failed to occur after 21 days of GnRH agonist therapy, the cycle was cancelled. Controlled ovarian stimulation was performed using highly purified urinary FSH (HP‐uFSH) (Fostimon, IBSA) at a starting dose which varied from 225 IU/day to 300 IU/day according to participant age, basal FSH level and antral follicle count. Following 5 days of HP‐uFSH therapy, dose adjustments were undertaken according to serum estradiol levels and follicle development. Once three or more follicles measuring more than 17 mm in diameter were identified on ultrasound, HP‐uFSH and Leuprorelin acetate were stopped and hCG (Pregnyl; N.V. Organon, OSS, Holland) was administered i.m. at a dose of 10,000 IU. Oocyte retrieval was performed with ultrasound guidance under deep sedation 36 ± 2 h following hCG administration.

Interventions

Group A: Following oocyte retrieval, an aspiration needle was inserted into the hydrosalpinx under ultrasound guidance to aspirate the hydrosalpingeal fluid, which was sent for microbiology analysis. Antibiotic prophylaxis was undertaken with a single dose of Azithromycin 1000 mg orally and 1 g Ceftriaxone i.m. given 2 h prior to oocyte retrieval.

Group B: no intervention.

Embryo transfer took place 3 days after oocyte retrieval (no more than three embryos transferred per cycle). A urine pregnancy test was performed at 2 weeks and an ultrasound examination carried out at 5 weeks after embryo transfer to diagnose clinical pregnancy. Luteal phase support was undertaken with progesterone vaginal capsules (Utrogestan, Safe Pharma, Egypt) at a dose of 20 mg three times daily, starting on the day of oocyte retrieval until fetal cardiac activity was identified on ultrasound at 5 weeks or pregnancy was ruled out by a negative beta‐hCG serum test.

Outcomes

1. Duration of stimulation (mean days ± SD)

2. Number of 75 IU HP‐uFSH ampoules consumed (mean ± SD)

3. Number of oocytes retrieved (mean ± SD)

4. Number of fertilised and cleaved oocytes (mean ± SD)

5. Number of embryos transferred (mean ± SD)

6. Grade I‐II/all embryos transferred (n/n, %)

7. Implantation rate (the ratio between the number of gestational sacs visible on ultrasound scan and the number of transferred embryos) (n/n, %)

8. Clinical pregnancy rate (presence of intrauterine gestational sac detected by transvaginal ultrasound) (n/n, %)

9. Ongoing pregnancy rate (pregnancy continuing after 20 weeks of gestation) (n/n, %)

10. Spontaneous miscarriage rate (miscarriage before 20 weeks of gestation) (n/n, %)

11. Ectopic pregnancy rate (implantation of the embryo outside the normal endometrial cavity) (n/n, %)

12. Flaring of pelvic infection (n/n, %)

Notes

The study was registered in clinicaltrials.gov (NCT01040351) on 28 December 2009.

Power calculation performed and followed.

The authors declared no conflict of interests.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Randomisation was achieved through computer generated randomization list"

Allocation concealment (selection bias)

Low risk

"sequentially numbered, opaque, otherwise identical sealed envelopes"

Blinding of participants and personnel (performance bias)
All outcomes

High risk

No blinding.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not specified.

Incomplete outcome data (attrition bias)
Intention to treat for primary outcome?

High risk

Loss to follow‐up was accounted for (a total of 3 women did not undergo ART following intervention or no intervention), however an intention to treat analysis was not performed.

Selective reporting (reporting bias)

Low risk

No suggestion of selective reporting.

Other bias

Low risk

No significant differences in participant characteristics.

Study characteristics

Methods

Parallel RCT

Participants

Country: Egypt

Site: Single centre ‐ Assisted conception unit of the Aljazeera (Al Gazeera) hospital, Giza, Egypt.

Participants: 160 patients with unilateral or bilateral hydrosalpinx visible on ultrasound, of which 80 were allocated to undergo uni‐ or bilateral laparoscopic salpingectomy and 80 underwent aspiration of hydrosalpinges under ultrasound guidance.

Mean age + SD: 28.14 + 3.67 (salpingectomy) and 27.55 + 3.52 (aspiration of hydrosalpinges).

Inclusion: women aged 18 to 37 years with unilateral or bilateral hydrosalpinges visible by ultrasound.

Exclusion: age < 18 and > 37 years; FSH ≥ 12 IU/L; uterine fibroids requiring surgical treatment; irregular menstrual cycles; previous IVF; BMI <19 or >30; endometriosis; recurrent pregnancy loss; and systemic disease contraindicating pregnancy.

IVF protocol: Controlled ovarian stimulation entailed administration the GnRH agonist triptorelin (Decapeptyl, Ipsen, Slough, United Kingdom) starting one week before the anticipated day of a menstrual period, at a dose of 0.1 mg/day. Pituitary down‐regulation was confirmed in those whose serum estradiol level was < 50 pg/mL and endometrial thickness < 5 mm on Day 3 of the next menstrual cycle. Highly purified urinary FSH (HP‐uFSH) (Fostimon, IBSA, Switzerland) was commenced once pituitary down‐regulation was confirmed, with a starting dose between 150 and 300 IU according to ovarian reserve indicators such as age, antral follicle count and basal FSH. The daily dose of HP‐uFSH was adjusted 5 days after starting stimulation depending on follicle development as assessed by ultrasound and serum estradiol levels. Both triptorelin and HP‐uFSH were continued up to and including the day of hCG (Pregnyl; N.V. Organon, Oss, The Netherlands) administration. When 3 or more follicles measuring ≥ 18 mm were identified on ultrasound, ovulation was triggered with 10000 IU hCG. Oocyte retrieval was performed under deep sedation and ultrasound guidance 34 to 36 hours after hCG administration. Both groups received Azithromycin 1000 mg orally and 1 g Cefotaxime i.m. prior to oocyte retrieval.

Embryo transfer (maximum 3 embryos) occurred on Day 2 or Day 3 post oocyte retrieval and serum hCG levels were measured 14 days after embryo transfer to diagnose pregnancy. An ultrasound was performed 5 weeks after embryo transfer to confirm pregnancy viability and count the number of gestational sacs in the uterine cavity.

Luteal phase support was provided with progesterone suppositories 200 mg twice daily (Prontogest, Marcyrl Pharmaceutical Industries, El Obour, Egypt) starting from the day of oocyte retrieval until 12 weeks of pregnancy or a negative pregnancy test.

Interventions

Women were allocated to undergo laparoscopic salpingectomy or aspiration of hydrosalpinges.

In the laparoscopic salpingectomy group, bilateral salpingectomy was performed using bipolar electrocoagulation, and proximal tubal occlusion with distal fenestration of hydrosalpinx was done in women with extensive pelvic adhesions instead of salpingectomy. A minimum period of 2 months was advised between surgery and oocyte retrieval.

Women in the aspiration group underwent aspiration of hydrosalpinx immediately following oocyte retrieval. An aspiration needle was inserted into the hydrosalpinx and suction was applied to aspirate the entirety of the fluid, which was sent for microbiology analysis. A maximum of 3 embryos were transferred per participant 2 or 3 days after oocyte retrieval.

Outcomes

1. Duration of stimulation (mean ± SD)

2. Number of HP‐uFSH units consumed (mean ± SD)

3. Number of follicles ≥ 18 mm on the day of hCG administration (mean ± SD)

4. Number of oocytes retrieved (mean ± SD)

5. Number of metaphase II oocytes (mean ± SD)

6. Number of embryos obtained (mean ± SD)

7. Number of embryos transferred (mean ± SD)

8. Fertilisation rate (n/n, %)

9. Grade I‐II/all embryos transferred (n/n, %)

10. Implantation rate (not defined) (n/n, %)

11. Clinical pregnancy rate per started cycle and per transfer cycle (presence of intrauterine gestational sac detected by transvaginal ultrasound) (n/n, %)

12. Ongoing pregnancy rate per started cycle and per transfer cycle (pregnancy continuing after 20 weeks of gestation) (n/n, %)

13. Spontaneous miscarriage rate (not defined) (n/n, %)

14. Ectopic pregnancy rate (not defined) (n/n, %)

15. Operative complications (not defined) (n/n, %)

16. Flaring of pelvic infection (n/n, %)

Notes

The study was registered in clinicaltrials.gov (NCT02008240) on 8 December 2013.

A power calculation was performed but not followed as the number calculated (1150 participants in each group) could not be achieved in the trial setting.

The authors declared no conflict of interests.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"computer generated randomization list"

Allocation concealment (selection bias)

Low risk

"sequentially numbered sealed envelopes"

Blinding of participants and personnel (performance bias)
All outcomes

High risk

No blinding.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not specified.

Incomplete outcome data (attrition bias)
Intention to treat for primary outcome?

Low risk

No loss to follow‐up.

Selective reporting (reporting bias)

Low risk

No suggestion of selective reporting.

Other bias

Low risk

No significant differences in participant characteristics.

Study characteristics

Methods

Parallel RCT

Participants

Country: United Kingdom

Site: Single centre ‐ Assisted Conception Unit (ACU) of Birmingham Women's Hospital, United Kingdom.

Participants: 66 women with unilateral or bilateral hydrosalpinges diagnosed by ultrasound during controlled ovarian stimulation, of which 32 were allocated to undergo ultrasound‐guided aspiration of hydrosalpinx and 34 were allocated to the control group (no aspiration).

Mean age ± SD: 33.4 ± 4.5 (aspiration) and 33.9 ± 4.7 (no aspiration).

Inclusion: healthy women ≤ 39 years with an ultrasound diagnosis of uni‐ or bilateral hydrosalpinges during controlled ovarian stimulation or who were on the waiting list for elective salpingectomy prior to undergoing IVF.

Exclusion: not specified.

IVF protocol described in Hughes 1992.

Interventions

Participants allocated to the aspiration group underwent transvaginal ultrasound‐guided aspiration of hydrosalpinx immediately following oocyte collection, under deep sedation. The aspiration needle was inserted into the hydrosalpinx and suction applied to achieve complete drainage of the fluid contained in the fallopian tube(s) as confirmed by ultrasound, and hydrosalpinx fluid was sent for microbiology culture and sensitivity. In women with bilateral hydrosalpinges, the procedure was performed on both tubes with different sterile needles on each side to avoid cross‐contamination. Antibiotic cover was provided with the intraoperative administration of i.v. amoxicillin 1 g and clavulanic acid 200 mg (or metronidazole 400 mg three times daily for 5 days in those allergic to penicillin), followed by oral azithromycin 500 mg once daily for three days postoperatively.

Outcomes

1. Number of oocytes collected (mean ± SD)

2. Number of oocytes fertilised (mean ± SD)

3. Implantation rate (number of gestational sacs on ultrasound divided by the number of embryos transferred) (n/n, %)

4. Biochemical pregnancy per randomised woman (urinary hCG test performed 14 days after ET) (n/n, %)

5. Clinical pregnancy per randomised woman (gestational sac visualized on transvaginal ultrasound) (n/n, %)

6. Miscarriage rate per biochemical pregnancy (pregnancy loss before 12 weeks of gestation) (n/n, %)

7. Ectopic pregnancy rate (not defined) (n/n, %)

8. Pelvic infection rate (pelvic abdominal pain and pyrexia or positive culture of genital swabs) (n/n, %)

Notes

This trial was prospectively registered (NCT00566956).

A power calculation was performed but not followed as the number calculated (total 158 women, 79 participants per group) could not be achieved in 3 years and the trial was stopped after nearly 4 years of recruitment as several women opted for salpingectomy instead.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"computer algorithm"

Allocation concealment (selection bias)

Low risk

Randomisation by computer algorithm using a third party administrator just prior to oocyte retrieval procedure.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

No blinding.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not specified.

Incomplete outcome data (attrition bias)
Intention to treat for primary outcome?

Low risk

Intention to treat analysis performed (as there were no drop‐outs or losses).

Selective reporting (reporting bias)

Low risk

No suggestion of selective reporting.

Other bias

Low risk

Both groups were comparable in terms of age, cause of infertility and stimulation regimen.

Study characteristics

Methods

Parallel RCT

Participants

Country: Greece

Site: Two centres in Athens ‐ Second Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital; and the Centre for Human Reproduction.

Participants: 115 patients randomised to one of three groups ‐ 50 underwent unilateral or bilateral laparoscopic proximal tubal occlusion before IVF (Group A); 50 underwent laparoscopic unilateral or bilateral salpingectomy before IVF (Group B); and 15 received no intervention prior to IVF (Group C).

Mean age ± SD: 31 ± 4.5 (Group A), 29.8 ± 3.4 (Group B), 34 ± 5.3 (Group C).

Inclusion: women aged ≤ 41 years with unilateral or bilateral hydrosalpinges confirmed by HSG and Day 2/3 FSH levels ≤ 12 mIU/mL; presence of spermatozoa in semen; suitability for IVF/ICSI treatment; no contraindication for laparoscopic surgery; no previous IVF attempt; no other pelvic pathology.

Exclusion criteria: not specified.

IVF protocol: women in groups A and B underwent IVF treatment once two completed menstrual cycles had passed since surgery. All subjects receiving IVF underwent controlled ovarian stimulation with a long protocol. Down‐regulation was achieved with a GnRH analogue administered s.c. from the midluteal phase of the previous cycle; stimulation ensued with recombinant FSH administered s.c. at a daily dose of 150 to 300 IU based on serial ultrasound measurements of follicle growth and serum estradiol quantification. Oocyte retrieval was performed 35 h after the administration of 10000 of hCG. Embryo transfers were performed on Day 3, and the number of embryos transferred varied according to the woman's age and embryo availability/quality.

Luteal phase support entailed the vaginal administration of progesterone 600 mg daily; oral doxycycline 100 mg twice daily for 6 days following oocyte retrieval; and oral prednisolone 5 mg three times per day for 6 days following oocyte retrieval.

Interventions

Women in Group A underwent laparoscopic unilateral or bilateral salpingectomy by transection of the mesosalpinx as close to the fallopian tube as possible. The tube was then removed at 1‐1.5 cm from the cornual junction.

Laparoscopic proximal tubal occlusion was performed in patients in Group B by applying bipolar diathermy to the isthmic segment at two separate sites, without draining the hydrosalpinx.

Outcomes

1. Number of collected oocytes (mean ± SD)

2. Number of fertilised oocytes (mean ± SD)

3. Implantation rate (implanted sacs per hundred transferred embryos) (%)

4. Clinical pregnancy rate (gestational sac ± fetal pole confirmed by ultrasound 4 weeks after embryo transfer, calculated per hundred transfers) (%)

5. Ongoing pregnancy rate (pregnancies beyond the first trimester, calculated per hundred transfers) (%)

6. Miscarriage rate (not defined) (%)

7. Ectopic pregnancy rate (not defined) (%)

Notes

The authors did not specify a trial registration number.

A power calculation was performed and followed.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"computer generated randomization in blocks"

Allocation concealment (selection bias)

Unclear risk

Not specified.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not specified. The previous version of the review states: "The operator and the IVF performer were the same person in some cases".

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not specified.

Incomplete outcome data (attrition bias)
Intention to treat for primary outcome?

High risk

112 women analysed of 115 randomised.

Group A: 2 women did not proceed to IVF treatment after tubal occlusion.

Group B: 1 woman did not proceed to IVF treatment after salpingectomy.

Intention to treat analysis not explicitly stated.

Selective reporting (reporting bias)

Low risk

No suggestions of selective outcome reporting.

Other bias

Low risk

There were no significant differences in demographic characteristics between groups.

Study characteristics

Methods

Parallel RCT

Participants

Country: Egypt

Site: single centre ‐ Ain Shams University Maternity Hospital, Egypt.

Participants: 82 patients with bilateral hydrosalpinx were randomised to undergo laparoscopic salpingectomy (n = 41) or proximal tubal occlusion and division (n = 41).

Mean age ± SD: 29.4 ± 3.19 years (salpingectomy group) and 30.14 ± 3.14 years (tubal occlusion and division group).

Inclusion: age 25 to 35 years; regular menstrual cycles; no previous abdominal surgery; HSG findings of bilateral hydrosalpinges; normal baseline hormonal profile; previous one or more failed trials of IVF‐ET.

Exclusion: age < 25 or > 35 years; previous laparoscopy or laparotomy; known ovulatory dysfunction due to polycystic ovary syndrome; presence of endometriosis.

IVF protocol: all patients underwent a long GnRH agonist protocol according to local practice. No further details provided by the authors.

Interventions

Laparoscopic salpingectomy VERSUS proximal tubal occlusion and division.

Laparoscopic salpingectomy was performed using bipolar diathermy. The mesosalpinx was transected just below the fallopian tube to minimize any compromise to the collateral blood supply of the ipsilateral ovary. Adhesiolysis was also performed.

Laparoscopic tubal occlusion and division entailed transection of the fallopian tube 1 to 1.5 cm from the cornual end. Proximal tubal occlusion was performed using bipolar diathermy applied at two sites separated by ~1cm on the isthmic portion of the affected tube, and the hydrosalpinx was not drained.

Outcomes

1. Serum AMH levels pre‐ and post‐intervention (units not specified)

2. Ongoing pregnancy rate (fetal heartbeat seen on ultrasound at 10 weeks of gestation) (n/n) ‐ extrapolated as clinical pregnancy for the purposes of meta‐analysis

Notes

This is a conference abstract, and additional information was provided by the first author via written correspondence.

The authors did not specify a trial registration number.

A power calculation was performed and a total of 84 women were required. However, the authors report a sample of 82 women only (41 randomly allocated to each group).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation was performed using a computer‐generated randomisation system as clarified by written correspondence from the first author.

Allocation concealment (selection bias)

Low risk

Allocation was blinded, as clarified by written correspondence from the first author.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Correspondence with the authors revealed that no blinding was undertaken.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not specified.

Incomplete outcome data (attrition bias)
Intention to treat for primary outcome?

Low risk

There was no loss to follow‐up. Analyses were performed according to the intention to treat principle.

Selective reporting (reporting bias)

Low risk

No suggestion of selective outcome reporting.

Other bias

Unclear risk

Not specified.

Study characteristics

Methods

Parallel RCT

Participants

Country: Moldova

Site: single academic centre ‐ Center for Reproductive Health and Genetics, Chisinau, Moldova.
Participants: 204 patients recruited, randomised and analysed (Group 1 ‐ 66 women randomised to no surgical treatment; Group 2 ‐ 60 women randomised to salpingectomy; Group 3 ‐ 78 randomised to proximal tubal occlusion); each woman underwent one cycle of IVF as stated by the authors.

Age: mean/median not specified; range 22 to 35 years.

Inclusion: women with hydrosalpinges diagnosed by ultrasound.
Exclusion: not specified.

IVF protocol: Ovarian stimulation in a long course GnRH analogue protocol (Decapeptyl or Dipherelin) with a fixed dose (225 IU daily) of recombinant FSH for stimulation, starting on day 3 of the cycle. Ovarian response was monitored by ultrasound and serum E2 concentration. Ovulation was triggered with 10000 IU of hCG (Pregnyl) when the leading follicles reached 18 to 20 mm. Oocyte retrieval was carried out 36 hours after hCG administration. Retrieved oocytes were evaluated and fertilised by conventional insemination. Embryos were transferred on day 3 after insemination. Utrogestan 400 mg/day was administered vaginally from the day of oocyte pick‐up until 12th week of pregnancy.

Interventions

Salpingectomy versus proximal tubal clamping of hydrosalpinges versus no intervention. The authors did not specify whether salpingectomy was performed laparoscopically or via laparotomy. Additionally, no details on the tubal clamping procedure were provided.

Outcomes

1. Number of oocytes retrieved (mean ± SD)

2. Number of fertilised oocytes (mean ± SD)

3. Clinical pregnancy ‐ gestational sac on ultrasound (n/n, %)

Notes

As data extraction on the abstract was limited, queries were resolved by contacting the author for the previous version of this review.

The authors did not specify a trial registration number.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not specified.

Allocation concealment (selection bias)

Low risk

By opaque numbered envelopes.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not specified.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not specified.

Incomplete outcome data (attrition bias)
Intention to treat for primary outcome?

Low risk

Not stated in abstract, but the number of patients randomised was the same as the number of patients analysed. Previous correspondence clarified there was no loss to follow‐up or withdrawal.

Selective reporting (reporting bias)

Low risk

No suggestions of selective reporting.

Other bias

Unclear risk

Not specified.

Study characteristics

Methods

Parallel RCT

Participants

Country: Denmark, Iceland and Sweden

Site: Multicentre trial conducted across 9 Nordic IVF sites.

Participants: 204 women with hydrosalpinx were included and randomised to undergo either laparoscopic salpingectomy or no intervention prior to IVF.

Age (mean ± SD): 31.8 ± 3.6 years (laparoscopic salpingectomy group) and 31.8 ± 3.7 years (no intervention group).

Inclusion: presence of unilateral or bilateral hydrosalpinges as diagnosed by HSG or laparoscopy; suitability for IVF treatment; no contraindications to laparoscopy; age < 39 years at the time of randomisation.

Exclusion: previous IVF treatment and the presence of cavity‐distorting uterine fibroids; male‐factor infertility requiring ICSI was accepted in centres where conventional IVF and ICSI success rates were identical.

IVF protocol: although regimens varied between centres, a long protocol with GnRH‐agonist given nasally or s.c. was generally used, followed by controlled ovarian stimulation with either HMG of HP‐/rFSH. Transvaginal ultrasound‐guided oocyte retrieval ensued. Although not more than 2 embryos were routinely transferred, this was occasionally increased to 3.

Interventions

Laparoscopic unilateral or bilateral salpingectomy was performed in the intervention group, depending on whether one or two hydrosalpinges were identified. Where technical difficulties were encountered (e.g. due to extensive adhesions), a proximal ligation and distal fenestration was performed instead. While in the intervention group 2 months were advised between surgery and IVF treatment in order to allow for the wash‐out of hydrosalpingeal fluid, in the control group women underwent ART immediately following randomisation.

Outcomes

1. Number of collected oocytes (mean ± SD)

2. Number of fertilised oocytes (mean ± SD)

3. Implantation rate ‐ number of gestational sacs on ultrasound divided by the number of embryos transferred

4. Ongoing pregnancy (pregnancy > 20 weeks) or delivery rate in first cycle per woman included, per started cycle, and per transfer cycle (n/n, %)

5. Pregnancy rate per woman included, per started cycle and per transfer cycle (n/n, %)

6. Clinical pregnancy rate (visible on ultrasound) per woman included, per started cycle and per transfer cycle (n/n, %)

7. Ectopic pregnancy rate per implanted embryo and per clinical pregnancy (n/n, %)

8. Miscarriage rate (not defined) per clinical pregnancy (n/n, %)

Notes

A subsequent analysis of cumulative data obtained from subsequent cycles in both groups was published by the trialists in 2001. Although an intention‐to‐treat analysis was performed in the follow‐up data, 24 women who had initially been assigned to the control group eventually underwent surgery after failed IVF cycles and thus their outcomes were not included in this review.

The authors did not specify a trial registration number.

A power calculation was performed but not followed as the sample size required (300) could not be reached within the duration of the study.

The study was supported by grants from the Göteborg Medical Society, the Hjalmar Svensson Foundation and a society named "Ordensällskapet W:6".

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation performed with sealed opaque envelopes in blocks of 10 to 30.

Allocation concealment (selection bias)

Low risk

Randomisation performed with sealed opaque envelopes in blocks of 10 to 30.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

No blinding was performed.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not specified.

Incomplete outcome data (attrition bias)
Intention to treat for primary outcome?

Low risk

An intention‐to‐treat analysis was performed.

Selective reporting (reporting bias)

Low risk

No suggestions of selective reporting.

Other bias

Low risk

There were no significant differences in baseline characteristics between groups apart from the rate of bilateral hydrosalpinges at inclusion, which was higher in the salpingectomy group (59% versus 41%, P = 0.02).

Study characteristics

Methods

Parallel RCT

Participants

Country: India

Site: single centre ‐ Reproductive Medicine Unit, Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India.

Participants: 165 women with bilateral hydrosalpinges were randomised into two groups. Group A included 83 patients who underwent laparoscopic bilateral proximal tubal occlusion; Group B included 82 women who underwent laparoscopic bilateral salpingectomy. There was no control group.

Mean age ± SD: 29.3 ± 2.6 years (Group A ‐ proximal tubal occlusion) and 29.4 ± 3.2 (Group B ‐ laparoscopic bilateral salpingectomy).

Inclusion: women with bilateral hydrosalpinx diagnosed by HSG or ultrasound; age < 39 years; normal uterine cavity.

Exclusion: history of endometriosis; prior ovarian surgery; polycystic ovary syndrome; poor ovarian reserve (FSH > 12 mIU/ml, AMH < 1.0 ng/ml);, adenomyosis; uterine synechiae; and a thin endometrium affecting implantation (not defined).

IVF protocol: IVF cycles were undertaken within 12 weeks of tubal surgery. All women underwent a long protocol of pituitary downregulation with GnRH agonist (Leuprolide‐Luprofact, Cadila Healthcare Ltd, Ahmedabad, India) at a daily dose of 0.5 mg from day 21 of the previous cycle. Complete pituitary desensitisation was assessed 14 days after starting GnRH‐agonist and confirmed where serum estradiol < 50 pg/mL, LH < 3 IU/L, no follicles > 10 mm in diameter and endometrial thickness < 5 mm on ultrasound. Recombinant FSH (Gonal F; Merck Serono, Mumbai, India) was administered at a dose of 150 to 300 IU/day varying in accordance to patient age, BMI, AFC and serum AMH. Serial follicle tracking was undertaken to monitor ovarian response and adjust gonadotrophin doses as required. Ovulation was triggered with recombinant hCG (250 mcg, Ovitrel; Merck Serono, Mumbai, India) when at least 3 follicles measuring ≥ 18 mm were identified on ultrasound. Oocyte retrieval was performed 36 hours after maturation trigger, and conventional IVF or ICSI was performed. A fertilisation check was done 16 to 18 hours after insemination, and up to a maximum of 2 good‐quality embryos were transferred on Day 3 or 5 under ultrasound guidance. Progesterone 100 mg i.m. (Susten, Sun Pharma, India) was administered daily for luteal support. Serum beta hCG was checked 16 days after embryo transfer and those with a positive result underwent ultrasound 4 weeks after transfer.

Interventions

Group A underwent laparoscopic bilateral proximal tubal occlusion by applying bipolar diathermy to the isthmic segment at two separate sites. Hydrosalpinges were not drained.

Group B underwent laparoscopic bilateral salpingectomy by transecting the fallopian tubes 1 cm away from the cornual end with bipolar diathermy.

Outcomes

1. Change in ovarian reserve parameters (FSH, AMH, estradiol and antral follicle count)

2. Total dose of gonadotrophins (median, IQR)

3. Oocytes retrieved (mean ± SD)

4. Fertilisation rate (mean ± SD)

5. Cleavage rate (mean ± SD)

6. Implantation rate (number of gestational sacs identified on ultrasound divided by the number of embryos transferred) (n/n, %)

7. Clinical pregnancy rate (presence of a gestational sac with a fetal pole and cardiac activity on TV‐US at 6 weeks) (n/n, %)

8. Live birth rate per cycle (n/n, %)

9. Miscarriage rate (pregnancy losses < 20 weeks of gestation) (n/n, %)

Notes

Additional trial design and outcome data were obtained through correspondence with the trial authors.

This trial was prospectively registered (CTRI/2016/08/007220).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Computer‐generated random numbers"

Allocation concealment (selection bias)

Unclear risk

Not specified.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

IVF personnel were blinded as to which surgical intervention participants had undergone prior to ART.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not specified.

Incomplete outcome data (attrition bias)
Intention to treat for primary outcome?

Low risk

Loss of follow‐up was accounted for. Although 6 women allocated to undergo laparoscopic salpingectomy could not receive the intervention due to dense adhesions, an intention‐to‐treat analysis was performed on both groups.

Selective reporting (reporting bias)

Low risk

There was no suggestion of selective reporting.

Other bias

High risk

Both groups were comparable in terms of age, BMI, type of infertility, duration of infertility, history of genital tuberculosis, ovarian reserve parameters and stimulation regimen.

A power calculation was performed but not followed as the number calculated (total 660 women, 330 patients per group) could not be achieved in a single centre. Recruitment was hence stopped prematurely.