Tratamiento quirúrgico para la enfermedad tubárica en mujeres a las que se les realizará fecundación in vitro
Resumen
Antecedentes
La enfermedad tubárica es responsable del 20% de los casos de infertilidad. El hidrosalpinge o hidrosálpinx, causado por la oclusión tubárica distal que da lugar a la acumulación de líquido en una o en las dos trompas, es una forma particularmente grave de enfermedad tubárica que afecta negativamente a los resultados de la tecnología de reproducción asistida (TRA). Se cree que la cirugía tubárica puede mejorar el resultado de las TRA en las mujeres con hidrosalpinge.
Objetivos
Evaluar la efectividad y la seguridad de la cirugía tubárica en mujeres con hidrosalpinge antes de someterse a una fecundación in vitro (FIV) o a una inyección intracitoplasmática de espermatozoides (ICSI) convencionales.
Métodos de búsqueda
Se hicieron búsquedas en el registro de ensayos del Grupo Cochrane de Ginecología y Fertilidad (Cochrane Gynaecology and Fertility Group [CGFG]), en CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL y en dos registros de ensayos hasta el 8 de enero de 2020; además se verificaron las referencias y se estableció contacto con los autores de los estudios y expertos en el ámbito para identificar más estudios.
Criterios de selección
Ensayos controlados aleatorizados (ECA) que compararon el tratamiento quirúrgico versus ningún tratamiento quirúrgico, o que compararon intervenciones quirúrgicas entre sí, en mujeres con enfermedad tubárica antes de someterse a FIV.
Obtención y análisis de los datos
Se utilizaron los procedimientos metodológicos estándar de Cochrane. Los desenlaces principales fueron la tasa de nacidos vivos (TNV) y la tasa de complicaciones quirúrgicas por mujer asignada al azar. Los desenlaces secundarios incluyeron las tasas de embarazo clínico, múltiple y ectópico, las tasas de aborto espontáneo y el número medio de ovocitos recuperados y embriones obtenidos.
Resultados principales
Se incluyeron 11 ECA con diseño paralelo, con 1386 participantes. Los ensayos incluidos compararon diferentes tipos de cirugía tubárica (salpingectomía, oclusión tubárica o aspiración transvaginal del líquido hidrosalpíngeo) con ninguna cirugía tubárica, o intervenciones individuales entre sí. Ningún estudio se evaluó como bajo riesgo de sesgo en todos los dominios; las principales limitaciones fueron la falta de cegamiento, los intervalos de confianza amplios y el reducido tamaño muestral y número de los episodios. Se utilizó la metodología GRADE para calificar la calidad de la evidencia. Aparte de un resultado de calidad moderada en una comparación de la revisión, la evidencia proporcionada por estos 11 ensayos varió de muy baja a baja.
Salpingectomía versus ninguna cirugía tubárica
Ningún estudio incluido informó sobre la TNV para esta comparación. No se conoce con certeza el efecto de la salpingectomía sobre las complicaciones quirúrgicas como la tasa de conversión a laparotomía (odds ratio [OR] de Peto 5,80; intervalo de confianza [IC] del 95%: 0,11 a 303,69; un ECA; n = 204; evidencia de calidad muy baja) y la infección pélvica (OR de Peto 5,80; IC del 95%: 0,11 a 303,69; un ECA; n = 204; evidencia de calidad muy baja). La salpingectomía probablemente aumenta la tasa de embarazo clínico (TEC) versus ninguna cirugía (riesgo relativo [RR] 2,02; IC del 95%: 1,44 a 2,82; cuatro ECA; n = 455; I2 = 42,5%; evidencia de calidad moderada). Lo anterior indica que en las mujeres con una TEC de aproximadamente el 19% sin cirugía tubárica, la tasa con salpingectomía se encuentra entre el 27% y el 52%.
Oclusión tubárica proximal versus ninguna cirugía
Ningún estudio informó sobre la tasa de complicaciones quirúrgicas ni sobre la TNV para esta comparación. La oclusión tubárica puede aumentar la TEC en comparación con ninguna cirugía tubárica (RR 3,21; IC del 95%: 1,72 a 5,99; dos ECA; n = 209; I2 = 0%; evidencia de calidad baja). Lo anterior indica que con una TEC de aproximadamente el 12% sin cirugía tubárica, la tasa con oclusión tubárica se encuentra entre el 21% y el 74%.
Aspiración transvaginal del líquido hidrosalpíngeo versus ninguna cirugía
Ningún estudio informó sobre la TNV para esta comparación, y no hubo evidencia suficiente para identificar una diferencia en la tasa de complicaciones quirúrgicas entre los grupos (OR de Peto no estimable; un ECA; n = 176). No se conoce con certeza si la aspiración transvaginal del líquido hidrosalpíngeo aumenta la TEC en comparación con ninguna cirugía tubárica (RR 1,67; IC del 95%: 1,10 a 2,55; tres ECA; n = 311; I2 = 0%; evidencia de calidad muy baja).
Oclusión tubárica proximal laparoscópica versus salpingectomía laparoscópica
No se conoce con certeza el efecto de la oclusión tubárica proximal laparoscópica versus la salpingectomía laparoscópica sobre la TNV (RR 1,21; IC del 95%: 0,76 a 1,95; un ECA; n = 165; evidencia de calidad muy baja) y la TEC (RR 0,81; IC del 95%: 0,62 a 1,07; tres ECA; n = 347; I2 = 77%; evidencia de calidad muy baja). Ningún estudio informó sobre la tasa de complicaciones quirúrgicas para esta comparación.
Aspiración transvaginal de líquido hidrosalpíngeo versus salpingectomía laparoscópica
Ningún estudio informó sobre la TNV para esta comparación, y no hubo evidencia suficiente para identificar una diferencia en la tasa de complicaciones quirúrgicas entre los grupos (OR de Peto no estimable; un ECA; n = 160). No se conoce con certeza el efecto de la aspiración transvaginal del líquido hidrosalpíngeo versus la salpingectomía laparoscópica en la TEC (RR 0,69; IC del 95%: 0,44 a 1,07; un ECA; n = 160; evidencia de calidad muy baja).
Conclusiones de los autores
Se encontró evidencia de calidad moderada de que la salpingectomía previa a la TRA probablemente aumenta la TEC, en comparación con ninguna cirugía, en las mujeres con hidrosalpinge. Al comparar la oclusión tubárica con ninguna intervención, se encontró que la oclusión tubárica puede aumentar la TEC, aunque la evidencia fue de calidad baja. No se encontró evidencia suficiente de un efecto sobre los episodios adversos relacionados con el procedimiento o el embarazo cuando se comparó la cirugía tubárica con ninguna intervención. Es importante señalar que ninguno de los estudios informó sobre los desenlaces de fertilidad a largo plazo. Se necesitan más ensayos de alta calidad para determinar definitivamente la repercusión de la cirugía tubárica en la FIV y los resultados del embarazo de las mujeres con hidrosalpinge, en particular para la TNV y las complicaciones quirúrgicas; y para investigar la eficacia y la seguridad relativas de las diferentes modalidades quirúrgicas en el tratamiento del hidrosalpinge antes de las TRA.
PICOs
Resumen en términos sencillos
Tratamiento quirúrgico para la enfermedad tubárica en mujeres a las que se les realizará fecundación in vitro
Pregunta de la revisión
Se examinó la eficacia y la seguridad de realizar una cirugía en mujeres con enfermedad conocida de las trompas de Falopio, en particular el hidrosalpinge (una afección en la que el líquido se acumula en una o ambas trompas de Falopio, y que da lugar a resultados reproductivos deficientes), antes de la fecundación in vitro (FIV) y la inyección intracitoplasmática de espermatozoides (ICSI). El objetivo fue comparar todos los tipos de cirugía en las trompas de Falopio con ninguna cirugía antes de la FIV. Este tipo de cirugía incluye la salpingectomía, en la que se extrae una o ambas trompas de Falopio; la oclusión tubárica, en la que las trompas de Falopio se bloquean con clips metálicos o se separan con tijeras y electrocauterización para que el líquido de los hidrosalpinges existentes no llegue a la cavidad del útero; y la aspiración guiada por ultrasonido del líquido hidrosalpíngeo a través de la vagina. Cuando hubo evidencia disponible también se intentó comparar cualquier tipo de cirugía de las trompas de Falopio con cualquier otro tipo de cirugía de las trompas de Falopio.
Antecedentes
La obstrucción de una o ambas trompas de Falopio se diagnostica en hasta una de cada cinco mujeres que sufren de infertilidad. Para las mujeres con enfermedades de las trompas se utiliza el tratamiento de FIV, ya que los óvulos y los espermatozoides se manipulan fuera del cuerpo. Los embriones resultantes se transfieren de nuevo a la cavidad del útero, sin necesidad de que las trompas de Falopio estén abiertas. Sin embargo, los estudios de investigación han demostrado que en los casos de obstrucción de las trompas, las mujeres pueden desarrollar una afección llamada hidrosalpinge en la que se acumula líquido dentro de las trompas, lo que puede impedir la implantación exitosa de los embriones creados mediante FIV. Por lo tanto, se ha recomendado la cirugía tubárica para tratar los hidrosalpinges, ya que puede impedir que el líquido acumulado llegue a la cavidad del útero. Si este líquido llega a la cavidad del útero puede afectar negativamente el éxito de la concepción asistida.
Características de los estudios
Se encontraron 11 ensayos controlados aleatorizados que compararon la cirugía en las trompas de Falopio con ninguna cirugía tubárica, en 1386 mujeres con hidrosalpinges antes de la FIV. La evidencia está actualizada hasta enero de 2020.
Resultados clave
Ningún estudio informó sobre las tasas de nacidos vivos en la comparación principal de cirugía tubárica versus ninguna cirugía tubárica. Comparada con ninguna cirugía en las trompas de Falopio, la salpingectomía probablemente aumenta la posibilidad de un embarazo clínico. La evidencia indica que si se supone que la probabilidad de embarazo clínico es del 19% sin salpingectomía, la probabilidad de embarazo clínico después de la salpingectomía estaría entre el 27% y el 52%. No hubo datos suficientes disponibles para identificar un efecto de los diferentes tipos de cirugía tubárica sobre los episodios adversos como las complicaciones quirúrgicas, los abortos y los embarazos ectópicos.
Calidad de la evidencia
Aparte de un desenlace de calidad moderada en una comparación de la revisión, la evidencia proporcionada por estos 11 ensayos varió de calidad muy baja a baja. Las principales limitaciones de la evidencia fueron la falta de cegamiento (proceso en el que las mujeres que participan en el ensayo, así como el personal de investigación, no están al tanto de la intervención utilizada), la inconsistencia (diferencias en los desenlaces entre los estudios) y la imprecisión (error al azar y tamaño pequeño de cada estudio).
Authors' conclusions
Summary of findings
| Tubal surgery compared to no surgery for tubal disease in women due to undergo in vitro fertilisation | ||||||
| Patient or population: tubal disease in women due to undergo in vitro fertilisation | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with no tubal surgery | Risk with tubal surgery | |||||
| Live birth rate | No studies reported on this outcome for the main comparison. | |||||
| Surgical complication rate | ||||||
| Salpingectomy (all methods) | 0 per 1,000 | 0 per 1,000 | Peto OR 5.80 | 204 | ⊕⊝⊝⊝ | We are uncertain of the effect of salpingectomy on the rate of conversion to laparotomy. |
| Surgical complication rate | ||||||
| Salpingectomy (all methods) | 0 per 1,000 | 0 per 1,000 (0 to 0) | Peto OR 5.80 (0.11 to 303.69) | 204 (1 RCT) | ⊕⊝⊝⊝ | We are uncertain of the effect of salpingectomy on the rate of pelvic infection. |
| Transvaginal aspiration of hydrosalpingeal fluid | 0 per 1,000 | 0 per 1,000 (0 to 0) | Not estimable | 176 (1 RCT) | ‐ | There were insufficient data to estimate differences between groups. |
| Clinical pregnancy rate | ||||||
| Salpingectomy (all methods) | 186 per 1,000 | 376 per 1,000 | RR 2.02 | 455 | ⊕⊕⊕⊝ | Salpingectomy probably increases clinical pregnancy rate. |
| Tubal occlusion (all methods) | 123 per 1,000 | 396 per 1,000 | RR 3.21 | 209 | ⊕⊕⊝⊝ | Tubal occlusion may increase clinical pregnancy rate. |
| Transvaginal aspiration of hydrosalpingeal fluid | 178 per 1,000 | 297 per 1,000 | RR 1.67 | 311 | ⊕⊝⊝⊝ | We are uncertain whether transvaginal aspiration of hydrosalpingeal fluid increases clinical pregnancy rate. |
| Miscarriage rate | ||||||
| Salpingectomy (all methods) | 53 per 1,000 | 48 per 1,000 | Peto OR 0.91 | 329 | ⊕⊕⊝⊝ | Salpingectomy may have little or no difference in miscarriage rate. |
| Tubal occlusion (all methods) | 67 per 1,000 | 40 per 1,000 | Peto OR 0.55 | 65 | ⊕⊝⊝⊝ | We are uncertain of the effect of tubal occlusion on miscarriage rate. |
| Transvaginal aspiration of hydrosalpingeal fluid | 44 per 1,000 | 56 per 1,000 | Peto OR 1.27 | 311 | ⊕⊝⊝⊝ | We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on miscarriage rate. |
| Ectopic pregnancy rate | ||||||
| Salpingectomy (all methods) | 23 per 1,000 | 8 per 1,000 | Peto OR 0.29 | 329 | ⊕⊕⊝⊝ | Salpingectomy may reduce ectopic pregnancy rate. |
| Tubal occlusion (all methods) | 0 per 1,000 | 0 per 1,000 | Peto OR 3.67 | 65 | ⊕⊝⊝⊝ | We are uncertain of the effect of tubal occlusion on miscarriage rate. |
| Transvaginal aspiration of hydrosalpingeal fluid | 15 per 1,000 | 10 per 1,000 | Peto OR 0.59 | 311 | ⊕⊝⊝⊝ | We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on ectopic pregnancy rate. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded one level for imprecision: wide confidence intervals. bDowngraded one level for imprecision: low number of participants. cDowngraded one level for risk of bias: at least one study with two domains at high risk of bias. dDowngraded one level for imprecision: single small study. | ||||||
| Laparoscopic proximal tubal occlusion versus laparoscopic salpingectomy for tubal disease in women due to undergo in vitro fertilisation | ||||||
| Patient or population: tubal disease in women due to undergo in vitro fertilisation | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with laparoscopic salpingectomy | Risk with proximal tubal occlusion | |||||
| Live birth rate | ||||||
| Laparoscopic proximal tubal occlusion vs laparoscopic salpingectomy | 268 per 1,000 | 325 per 1,000 | RR 1.21 | 165 | ⊕⊝⊝⊝ | We are uncertain of the effect of laparoscopic proximal tubal occlusion on live birth rate compared to laparoscopic salpingectomy. |
| Surgical complication rate | No study reported on this outcome for laparoscopic proximal tubal occlusion. | |||||
| Surgical complication rate | No study reported on this outcome for laparoscopic proximal tubal occlusion. | |||||
| Clinical pregnancy rate | ||||||
| Laparoscopic proximal tubal occlusion vs laparoscopic salpingectomy | 410 per 1,000 | 332 per 1,000 | RR 0.81 | 347 | ⊕⊝⊝⊝ | We are uncertain of the effect of laparoscopic proximal tubal occlusion on clinical pregnancy rate compared to laparoscopic salpingectomy. |
| Miscarriage rate | ||||||
| Laparoscopic proximal tubal occlusion vs laparoscopic salpingectomy | 30 per 1,000 | 23 per 1,000 | Peto OR 0.74 | 265 | ⊕⊕⊝⊝ | Laparoscopic proximal tubal occlusion may reduce miscarriage rate slightly compared to laparoscopic salpingectomy. |
| Ectopic pregnancy rate | ||||||
| Laparoscopic proximal tubal occlusion vs laparoscopic salpingectomy | 0 per 1,000 | 0 per 1,000 | Peto OR 7.39 | 100 | ⊕⊝⊝⊝ | We are uncertain of the effect of laparoscopic proximal tubal occlusion on ectopic pregnancy rate compared to laparoscopic salpingectomy. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded one level for imprecision: low number of participants. bDowngraded one level for imprecision: single small study. cDowngraded one level for imprecision: wide confidence intervals. dDowngraded one level for inconsistency: high degree of heterogeneity. | ||||||
| Transvaginal aspiration of hydrosalpinx versus laparoscopic salpingectomy for tubal disease in women due to undergo in vitro fertilisation | ||||||
| Patient or population: tubal disease in women due to undergo in vitro fertilisation | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with laparoscopic salpingectomy | Risk with transvaginal aspiration of hydrosalpingeal fluid | |||||
| Live birth rate | No studies reported on this outcome. | |||||
| Surgical complication rate | 0 per 1,000 | 0 per 1,000 | not estimable | 160 | ‐ | There were insufficient data to estimate differences between groups. |
| Clinical pregnancy rate | 400 per 1,000 | 276 per 1,000 | RR 0.69 (0.44 to 1.07) | 160 | ⊕⊝⊝⊝ | We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on clinical pregnancy rate compared to laparoscopic salpingectomy. |
| Miscarriage rate | 38 per 1,000 | 38 per 1,000 | Peto OR 1.00 (0.20 to 5.08) | 160 | ⊕⊝⊝⊝ | We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on miscarriage rate compared to laparoscopic salpingectomy. |
| Ectopic pregnancy rate | 0 per 1,000 | 0 per 1,000 | Peto OR 7.39 (0.15 to 372.38) | 160 | ⊕⊝⊝⊝ | We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on ectopic pregnancy rate compared to laparoscopic salpingectomy. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded one level for imprecision: low number of participants. bDowngraded one level for imprecision: single small study. cDowngraded one level for imprecision: wide confidence intervals. | ||||||
Background
Description of the condition
Infertility is common, affecting up to one in six heterosexual couples trying to conceive. Tubal pathology, whereby there is mechanical obstruction or altered function of one or both fallopian tubes, accounts for 20% of infertility cases and has many aetiologies including pelvic infection, previous abdominal surgery and endometriosis (Evers 2002; NICE 2013). In cases of distal tubal occlusion, fluid accumulation may occur inside the fallopian tube(s), leading to the formation of hydrosalpinx, which is considered to be the most severe form of tubal disease due to its negative impact upon both natural and assisted conception outcomes (Strandell 2002).
Rather than passively reducing fecundity, tubal disease may actively contribute to early reproductive failure (Chan 2002). Such a deleterious effect has been linked to different possible mechanisms, including the presence of molecules secreted by the tubal epithelium or contained in hydrosalpingeal fluid that are toxic to gametes and embryos (Bao 2017; Mukherjee 1996; Zeyneloglu 1998); an altered nutrient environment within the fallopian tube fluid affecting the early stages of embryogenesis (Bao 2017; Dickens 1995; Koong 1998; Tay 1997); an abnormal uterotubal flow leading to impaired fertilisation, endometrial receptivity and implantation (Cheng 2015; Eytan 2001; Meyer 1997; Zeyneloglu 1998); and a direct cytotoxic effect on the endometrium resulting from the leakage of hydrosalpingeal fluid through the uterine cavity, termed hydrorrhoea (Andersen 1996; Mansour 1991; Strandell 2002).
Assisted reproductive technology (ART), whereby human gametes and embryos are manipulated outside the body with the goal of achieving a pregnancy, was first developed to circumvent the tubal stages of fertilisation and early embryogenesis in women with fallopian tube pathology (Edwards 1984). Nevertheless, since the inception of in‐vitro fertilisation (IVF) there has been a growing body of evidence demonstrating a reduction in pregnancy rates, and an increased risk of early pregnancy loss, in women with tubal disease undergoing ART, particularly where hydrosalpinx is present (Bao 2017; Camus 1999; Chu 2015; Fleming 1996; Kassabji 1994; Strandell 1994; Vandromme 1995; Van Voorhis 2019; Zeyneloglu 1998). This has generated support towards treating hydrosalpinx prior to ART, although there remains a paucity of evidence on the relative efficacy and side‐effect profile of different treatment modalities (Aboulghar 1998; Lass 1999; Van Voorhis 2019).
Description of the intervention
There is no consensus on how to best manage women with tubal disease prior to IVF. In those with hydrosalpinx, treatment options aim to remove the detrimental effect of the hydrosalpingeal fluid by either aspirating it under ultrasound guidance; draining it by means of salpingostomy; isolating the hydrosalpinges from the uterine cavity via laparoscopic or hysteroscopic proximal tubal occlusion; or most often by removing the affected fallopian tube(s) altogether (salpingectomy).
How the intervention might work
Tubal surgery prior to ART mainly aims to remove the deleterious effect of hydrosalpingeal fluid upon embryo development and endometrial receptivity. Different surgical techniques have been employed to this effect, including salpingectomy, tubal occlusion, aspiration of hydrosalpingeal fluid and salpingostomy.
Salpingectomy remains the most commonly used treatment for hydrosalpinges, and the previous version of this review concluded that the odds of ongoing pregnancy (odds ratio (OR) 2.14, 95% confidence interval (CI) 1.23 to 3.73) and of clinical pregnancy (OR 2.31, 95% CI 1.48 to 3.62) were increased with laparoscopic salpingectomy for hydrosalpinges prior to IVF in comparison to no intervention (Johnson 2010). Salpingectomy is nonetheless invasive, irreversible and may be technically difficult to perform in women with dense pelvic adhesions (Dreyer 2016). Moreover, while a recent meta‐analysis of eight non‐randomised and randomised studies concluded that salpingectomy does not appear to reduce ovarian reserve (Mohamed 2017), there is evidence demonstrating that the ovarian response to controlled stimulation in ART may be impaired in women with a history of previous salpingectomy (Fan 2016; Gelbaya 2006; Lass 1998).
Tubal occlusion is perceived to be less invasive than salpingectomy and can be achieved via hysteroscopy (by inserting intratubal devices) or laparoscopy (by applying proximal tubal clips or cauterisation). Both approaches have been widely used in female sterilisation with high success rates (Hurskainen 2010; Smith 2010) and, more recently, in women with hydrosalpinx to prevent leakage of hydrosalpingeal fluid into the endometrial cavity prior to undergoing ART (Rosenfield 2005; Stadtmauer 2000). Nevertheless, the Essure® device, previously used for tubal occlusion to achieve sterilisation or treat hydrosalpinges, has been recently discontinued worldwide due to safety concerns (Horwell 2017).
Ultrasound‐guided transvaginal aspiration of hydrosalpingeal fluid has also been proposed as an alternative to salpingectomy as it is safe, less invasive and can be performed in an outpatient setting. However, the risk of hydrosalpinx recurrence within two weeks following aspiration has been shown to be as high as 30%, suggesting its long‐term effectiveness may be low (Hammadieh 2008).
Salpingostomy involves incising the fallopian tubes via laparoscopy or laparotomy, thus allowing for the drainage of fluid where hydrosalpinx is present. The benefits of salpingostomy include a low complication rate and the potential for future natural conception (Taylor 2001). Yet a recent systematic review demonstrated that although the live birth rate (LBR) achieved by natural conception following salpingostomy was 25%, the procedure carries a 10% risk of ectopic pregnancy (Chu 2015).
Why it is important to do this review
This review update stems from the need to establish which interventions are safest and most effective in achieving a live birth in women with hydrosalpinx prior to undergoing IVF. In addition to comparing the overall effect of all forms of tubal surgery versus no intervention, there is a need to investigate the relative effectiveness and safety of individual surgical modalities in head‐to‐head comparisons.
Crucially, since the previous version of this review, new randomised controlled data on live birth rates following salpingectomy and tubal occlusion have been published. It is therefore important to reappraise the available evidence in order to best inform women and clinicians when making management decisions.
Objectives
To assess the effectiveness and safety of tubal surgery in women with tubal disease prior to undergoing conventional IVF or intracytoplasmic sperm injection (ICSI).
Methods
Criteria for considering studies for this review
Types of studies
We included all published and unpublished randomised controlled trials (RCTs) comparing women undergoing surgical treatment for tubal disease prior to IVF with a control group receiving no intervention or any other form of surgical treatment. We planned to include cross‐over trials only if phase one data could be extracted. We excluded quasi‐randomised trials.
Types of participants
We included women with a known diagnosis of tubal disease (by means of diagnostic surgery or imaging such as simple ultrasound, hysterosalpingogram or hysterosalpingo‐contrast sonography) due to undergo IVF. There were no exclusion criteria.
Types of interventions
We included all studies where any surgical procedure performed unilaterally and/or bilaterally for tubal disease (such as salpingectomy, tubal occlusion, ultrasound guided/surgical aspiration of hydrosalpinx fluid or salpingostomy) was compared with any other tubal surgery, non‐surgical intervention or no intervention.
Types of outcome measures
Primary outcomes
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LBR per woman randomised, defined as the delivery of a live fetus after 22 completed weeks of gestational age (Zegers‐Hochschild 2017)
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Surgical complication rate per woman randomised, e.g. intraoperative bleeding or vasomotor instability, infection, need for repeat surgery or overall complications as reported by trialists
Secondary outcomes
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Clinical pregnancy rate (CPR) per woman randomised, defined as the presence of one or more gestational sacs on ultrasound (Zegers‐Hochschild 2017)
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Multiple pregnancy rate per woman randomised, defined as the number of twin, triplet or higher‐order pregnancies confirmed by ultrasound or delivery
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Miscarriage rate per woman randomised, defined as the spontaneous loss of an intrauterine pregnancy prior to 22 completed weeks of gestational age (Zegers‐Hochschild 2017)
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Ectopic pregnancy rate per woman randomised, defined as pregnancy outside the uterine cavity as diagnosed by ultrasound, surgical identification or histopathology (Zegers‐Hochschild 2017)
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Mean number of oocytes retrieved per woman randomised
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Mean number of embryos obtained per woman randomised
If outcomes were not reported as above, sufficient information had to be available to convert results to the outcomes stated above.
Search methods for identification of studies
We performed searches for all published and unpublished RCTs of women diagnosed with tubal disease receiving surgical treatment prior to IVF.
Electronic searches
We searched the following electronic databases;
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The Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register of Controlled Trials (PROCITE platform); searched 8 January 2020 (Appendix 1).
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Cochrane CENTRAL via the Cochrane Register of Studies Online (CRSO) web platform; searched 8 January 2020 (Appendix 2).
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MEDLINE; searched from 1946 to 8 January 2020 (OVID platform) (Appendix 3).
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Embase; searched from 1980 to 8 January 2020 (OVID platform) (Appendix 4).
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PsycINFO; searched from 1806 to 8 January 2020 (OVID platform) (Appendix 5).
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Cumulative Index to Nursing and Allied Health Literature (CINAHL); searched from 1961 to 8 January 2020 (EBSCO platform) (Appendix 6).
We combined the MEDLINE search with the Cochrane highly sensitive strategy for identifying randomised trials, which appears in Chapter 6 of the Cochrane Handbook for Systematic Reviews of Interventions (Lefebvre 2011). Embase and PsycINFO searches were combined with trial filters developed by the Scottish Intercollegiate Guidelines Network () (www.sign.ac.uk/what-we-do/methodology/search-filters/).
We searched the following additional sources of trials.
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Trial registers for ongoing and registered trials
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ClinicalTrials.gov, a service of the US National Institutes of Health (www.clinicaltrials.gov).
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World Health Organization International Clinical Trials Registry Platform search portal (www.who.int/trialsearch).
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DARE (Database of Abstracts of Reviews of Effects) in the Cochrane Library at onlinelibrary.wiley.com (for reference lists from relevant non‐Cochrane reviews).
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Web of Knowledge (wokinfo.com).
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OpenGrey; for unpublished reports from Europe (www.opengrey.eu).
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LILACS (Latin American and Caribbean Health Science Information Database); (regional.bvsalud.org).
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PubMed and Google (for recent trials not yet indexed in MEDLINE).
Searching other resources
In consultation with the Cochrane Gynaecology and Fertility (CGF) Group Information Specialist, we handsearched relevant journals and conference abstracts that were not covered by the above sources, without language restrictions,
Data collection and analysis
Selection of studies
Two review authors (PM and EXG) carried out an initial screen of titles and abstracts obtained by the searches and identified potentially eligible studies. We then retrieved the full text of all potentially eligible studies. Two review authors (PM and EXG) independently examined the full‐text articles for compliance with the inclusion criteria and selected studies eligible for inclusion in the review. We corresponded with study investigators as required to clarify study eligibility, and resolved disagreements about study eligibility by discussion or through arbitration by a third reviewer (IG). We documented the selection process using a Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) flow chart (Moher 2009) (Figure 1).
Study flow diagram.
Data extraction and management
Two review authors (PM and EXG) independently assessed study characteristics and methodological details of included studies and extracted data. We resolved differences in opinion by discussion between the two review authors or by consultation with a third review author (IG). Where studies had multiple publications, we assessed overlapping reports and collated them under a single study ID, with multiple references as required. Where we required additional information on trial methodology, original trial data or both, we contacted corresponding authors. We sent reminder correspondence, if we did not receive a reply within two weeks.
Assessment of risk of bias in included studies
Two review authors (PM and EXG) independently assessed the included studies for risk of bias using the Cochrane 'Risk of bias' assessment tool (Higgins 2011). We assessed the following parameters: allocation (random sequence generation and allocation concealment); performance (blinding of participants and personnel); detection (blinding of outcome assessors); attrition (incomplete outcome data); reporting (selective reporting); and other bias. We resolved differences in opinion by consultation with a third reviewer (IG). We described all judgements fully as presented in the 'Risk of bias' table, which has been incorporated into the interpretation of review findings by means of sensitivity analyses.
Measures of treatment effect
We performed statistical analyses according to Cochrane guidance. For dichotomous data (e.g. LBR) we used the number of events in the control and intervention groups of each study to calculate Mantel‐Haenszel risk ratios (RRs) with 95% CIs. We then combined these for meta‐analysis using RevMan 5.3 software and a fixed‐effect model. For outcomes with a small number of events, we used a Peto OR with its 95% CI instead. For continuous data, we calculated mean differences (MDs) or standardized mean difference (SMD) between treatment groups and presented these with 95% CIs for all outcomes.
Unit of analysis issues
The primary analysis was done per woman randomised. We planned to summarise in an additional table data that did not allow valid analysis (e.g. 'per cycle' or 'per pregnancy' data) but did not include these in the meta‐analysis. We counted multiple birth as a single live birth event. We planned to include only first‐phase data obtained from cross‐over trials. If studies reported only 'per cycle' data, we contacted study authors to request 'per woman randomised' data.
Dealing with missing data
We analysed data on an intention‐to‐treat (ITT) basis to the extent possible and attempted to obtain missing data from the original trialists. When data on live birth or clinical pregnancy were unobtainable, we assumed that the outcome did not occur. For other outcomes, we analysed only available data. We planned to subject any imputation to sensitivity analysis.
When studies reported sufficient data to allow calculation of MDs but provided no information on standard deviation (SD), we assumed that the outcome had an SD equal to the highest SD provided by other studies included in the same analysis.
Based on the extent to which data were missing, we explored the potential impact of the missing data on the results by sensitivity analysis.
Assessment of heterogeneity
We assessed statistical heterogeneity by measurement of the I2 statistic to determine whether clinical and methodological characteristics of the included studies were sufficiently similar for meta‐analysis. We considered an I2 measurement greater than 50% as an indicator of substantial heterogeneity (Higgins 2011). We explored substantial heterogeneity by conducting planned subgroup analyses as detailed below. We took any statistical heterogeneity into account when interpreting the results, especially if variation in the direction of effect was noted.
Assessment of reporting biases
We aimed to minimise the potential impact of publication bias and other reporting bias by ensuring a comprehensive search of multiple databases and grey literature. We planned that if 10 or more studies were included in the same analysis, we would produce a funnel plot to explore the impact of small‐study effects (a tendency for estimates of the intervention effect to be more beneficial in smaller studies) (Higgins 2011).
Data synthesis
We combined data from the primary studies using a fixed‐effect model for the comparison between different tubal surgery techniques or no surgical intervention prior to IVF.
If studies analysing individual surgical techniques were sufficiently similar (e.g. tubal occlusion, hydrosalpinx aspiration, salpingectomy) we combined and stratified the data using a fixed‐effect model in the following comparisons:
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Surgical treatment (all types) versus no surgery on the fallopian tube, followed by IVF. We stratified this according to the type of tubal surgery undertaken:
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Salpingectomy versus no intervention on the fallopian tube, followed by IVF;
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Occlusion of the fallopian tube versus no intervention on the fallopian tube, followed by IVF
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Hysteroscopic tubal occlusion versus no intervention on the fallopian tube
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Laparoscopic tubal occlusion versus no intervention on the fallopian tube;
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Aspiration of hydrosalpingeal fluid versus no surgery, followed by IVF;
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One tubal surgery modality (i.e. salpingectomy, tubal occlusion or aspiration of hydrosalpingeal fluid) versus any other type of tubal surgery.
In meta‐analyses, we graphically displayed an increase in the risk of a particular outcome that may be beneficial (e.g. LBR) or detrimental (e.g. adverse effects rate) to the right of the centre‐line and a decrease in the odds of an outcome to the left of the centre‐line.
Subgroup analysis and investigation of heterogeneity
Where data were available, we aimed to conduct a subgroup analysis to obtain separate evidence for primary outcomes within the following subgroups.
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Age: women aged <40 years or ≥40 years. Female age is the principal limiting factor of ART success and could have affected the reported pregnancy outcomes regardless of tubal disease.
Sensitivity analysis
We planned to conduct sensitivity analyses for the primary outcome measures to determine whether conclusions were robust to arbitrary decisions made regarding eligibility and analysis. These analyses were to include consideration of whether review conclusions would have differed if:
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eligibility had been restricted to studies at low risk of bias (i.e. no high or unclear risk of selection bias);
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a random‐effects model had been adopted;
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the unit of analysis had been per clinical pregnancy rather than per woman, for relevant outcomes (multiple pregnancy, miscarriage); or
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the summary effect measure was expressed as odds ratio rather than relative risk;
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studies with imputed results had been removed from the analysis.
Where we detected substantial heterogeneity, we explored clinical or methodological differences between or among studies that might have accounted for the heterogeneity.
Overall quality of the body of evidence: 'Summary of findings' table
We generated GRADE 'Summary of findings' (SoF) tables using GRADEpro software (GRADEpro GDT 2015). Two review authors (PM and EXG) prepared these tables, working independently. The two review authors resolved disagreements by discussion and consensus.
In using GRADE methodology, review authors considered several criteria to assess the quality of evidence for each outcome across the body of literature. These criteria include study limitations (i.e. risk of bias), consistency of effect, imprecision, indirectness and publication bias. On the basis of these criteria, we justified, documented and incorporated into the SoF tables our judgements about evidence quality (high quality, moderate quality, low quality or very low quality) for all outcomes.
Our SoF tables evaluated the overall quality of the body of evidence for the three main review comparisons (tubal surgery versus non‐surgical or no intervention prior to IVF; tubal occlusion versus laparoscopic salpingectomy; and transvaginal aspiration of hydrosalpingeal fluid versus laparoscopic salpingectomy), and report the main review outcomes (LBR, surgical complication rate, CPR, miscarriage rate and ectopic pregnancy rate).
Results
Description of studies
Results of the search
In the previous version of this review (Johnson 2010), the search strategy identified 103 potentially relevant citations. Five full‐text studies were included in the quantitative synthesis and meta‐analysis (Dechaud 1998; Hammadieh 2008; Kontoravdis 2006; Moshin 2006; Strandell 1999).
For this review update, our electronic searches on 8 January 2020 identified 1457 studies. We identified one additional article via ClinicalTrials.gov (www.clinicaltrials.gov). Following the removal of 280 duplicates, we screened the abstracts of 1178 articles, of which we excluded 1149 as they were clearly not relevant (Characteristics of excluded studies). Five studies were ongoing trials that had not yet reported their results (ChiCTR‐IOR‐16008961; IRCT2014011116161N1; ISRCTN40458453; NCT03521128; PACTR201709002555574) (Characteristics of ongoing studies). We assessed the full text of the remaining 24 studies and excluded 13 references for the following reasons: six were not RCTs (Bao 2016; Harb 2014; Kuzmin 2014; Mardesic 1999; Savic 1999; Yu 2018); two did not feature tubal surgery as an intervention (De Angelis 2010; Kang 2001); one did not focus on the patient population included in this review (Dias Pereira 1999); two did not report on IVF outcomes (Darwish 2006; Mossa 2005); and two studies are awaiting classification due to unclear design (Goldstein 1998) or because it was not clear what surgical intervention had been performed (Lindig 2002). The trialists did not respond to correspondence by the time of publication.
Eleven studies met the inclusion criteria for this review (An 2015; Dechaud 1998; Dreyer 2016; Fouda 2011; Fouda 2015; Hammadieh 2008; Kontoravdis 2006; Labib 2016; Moshin 2006; Strandell 1999; Vignarajan 2019) and were included in our quantitative meta‐analysis. We present the PRISMA study flow diagram in Figure 1.
Included studies
Study design and setting
The previous version of this review included a total of five RCTs and analysed the outcomes of 646 women (Dechaud 1998; Hammadieh 2008; Kontoravdis 2006; Moshin 2006; Strandell 1999). In this update, we included six additional parallel‐design RCTs (An 2015; Dreyer 2016; Fouda 2011; Fouda 2015; Labib 2016; Vignarajan 2019). Of the 11 trials included in the final meta‐analysis, nine have been published as full articles (An 2015; Dechaud 1998; Dreyer 2016; Fouda 2011; Fouda 2015; Hammadieh 2008; Kontoravdis 2006; Strandell 1999; Vignarajan 2019) and two as conference abstracts (Labib 2016; Moshin 2006). A total of 1386 women with tubal disease were analysed in this update on an intention‐to‐treat basis.
Of the included studies, two analysed the efficacy and adverse events of salpingectomy compared to no tubal surgery in women with hydrosalpinges prior to undergoing ART (Dechaud 1998; Strandell 1999); two compared transvaginal aspiration of hydrosalpingeal fluid versus no aspiration (Fouda 2011; Hammadieh 2008); two trials had three randomisation groups, assessing the effect of tubal occlusion in comparison with salpingectomy and no tubal surgery for hydrosalpinges (Kontoravdis 2006; Moshin 2006); three studies compared salpingectomy with tubal occlusion (Dreyer 2016; Labib 2016; Vignarajan 2019); and one article compared salpingectomy to transvaginal aspiration of hydrosalpingeal fluid (Fouda 2015). In one trial (An 2015), 217 women were randomised to one of three groups: Group A underwent transvaginal aspiration of hydrosalpinges in addition to auricular point sticking; Group B received transvaginal aspiration of hydrosalpinges alone; and Group C underwent no intervention. Only groups B and C were included in this analysis. We identified no studies comparing tubal occlusion with aspiration of hydrosalpingeal fluid. Furthermore, our searches did not identify any RCTs where one of the intervention arms underwent salpingostomy for the treatment of tubal disease prior to ART.
Eight of the included studies were single‐centre trials and were carried out in China (An 2015), Egypt (Fouda 2011; Fouda 2015; Labib 2016), France (Dechaud 1998), Moldova (Moshin 2006) and the United Kingdom (Hammadieh 2008). Of the three multicentre studies included, one was a multinational trial carried out in Denmark, Iceland and Sweden (Strandell 1999); and the remaining two were conducted in Greece (Kontoravdis 2006) and in the Netherlands (Dreyer 2016).
An 2015 was the largest trial included in this review, analysing 217 women. Dechaud 1998 was the smallest study, assessing 60 participants.
Loss to follow‐up occurred and was accounted for by An 2015 (n = 12), Dreyer 2016 (n = 4), Fouda 2011 (n = 3) and Kontoravdis 2006 (n = 3). There were no reported cases of loss to follow‐up in the trials by Dechaud 1998, Fouda 2015, Hammadieh 2008, Labib 2016, Moshin 2006, Strandell 1999 and Vignarajan 2019.
Participants
The 11 trials included in this review analysed a total of 1386 women with tubal disease. Of these, 502 underwent salpingectomy; 294 underwent tubal occlusion; 256 were subjected to transvaginal aspiration of hydrosalpingeal fluid; and 334 had no tubal surgery.
Participant age was stated in all of the included studies, and the upper age limit for inclusion did not exceed 41 years in any of the trials. There were no significant differences in the baseline characteristics between the study groups in the trials by Dechaud 1998, Fouda 2011, Fouda 2015, Hammadieh 2008, Kontoravdis 2006 and Vignarajan 2019. An 2015, Labib 2016 and Moshin 2006 did not refer to any differences in baseline characteristics between the trial groups, and did not provide additional details upon further correspondence with the trial authors. Strandell 1999 reported a significantly higher rate of bilateral hydrosalpinges amongst the salpingectomy group (P = 0.02) but no difference in all other baseline parameters such as age and rate of primary infertility.
The presence of unilateral or bilateral hydrosalpinges constituted an inclusion criterion in ten trials (An 2015; Dreyer 2016; Fouda 2011; Fouda 2015; Hammadieh 2008; Kontoravdis 2006; Labib 2016; Moshin 2006; Strandell 1999; Vignarajan 2019), while Dechaud 1998 also included women in whom features of salpingitis isthmica nodosa were identified by hysterosalpingogram (HSG) or laparoscopy.
An 2015, Dechaud 1998, Dreyer 2016 and Strandell 1999 diagnosed tubal disease either by HSG or laparoscopy; Kontoravdis 2006 diagnosed hydrosalpinges with HSG in all participants; Fouda 2011, Fouda 2015, Hammadieh 2008 and Moshin 2006 stated that a diagnosis of hysterosalpinges was made by ultrasound but did not specify whether contrast was used; Vignarajan 2019 diagnosed hydrosalpinges with HSG or transvaginal 2D ultrasound; and Labib 2016 did not specify how they diagnosed hydrosalpinges.
Of the included studies, three (Hammadieh 2008; Kontoravdis 2006; Strandell 1999) included couples with concurrent male factor infertility undergoing ICSI, although the proportions of these couples were similar in groups within the studies. Dreyer 2016 also included couples with male factor infertility, although only three participants underwent ICSI. On further correspondence, the study authors confirmed that none had severe male factor.
Three studies (Hammadieh 2008; Kontoravdis 2006; Moshin 2006) did not specify their exclusion criteria.
No subgroup analyses were prespecified apart from in the trial of Kontoravdis 2006, where IVF treatment outcomes were analysed in the subgroups of women with bilateral hydrosalpinges and ultrasound‐visible hydrosalpinges.
Ten studies (An 2015; Dechaud 1998; Fouda 2011; Fouda 2015; Hammadieh 2008; Kontoravdis 2006; Labib 2016; Moshin 2006; Strandell 1999; Vignarajan 2019) used gonadotropin‐releasing hormone (GnRH) agonists to achieve pituitary desensitisation, while Dreyer 2016 used GnRH agonists or antagonists. Except for Dechaud 1998 and Strandell 1999, all studies reported results over one IVF cycle, although only three trials (Dreyer 2016; Fouda 2011; Kontoravdis 2006) specifically stated that they analysed the first cycle following the allocated intervention.
With the exception of three trials (An 2015; Labib 2016; Moshin 2006), all studies reported on the timing of IVF after the intervention. Of the trials assessing efficacy of salpingectomy or tubal occlusion, four (Dreyer 2016; Kontoravdis 2006; Moshin 2006; Strandell 1999) had a time interval from surgery to IVF of at least two to three months, while in the trial by Vignarajan 2019 IVF was performed no later than 12 weeks following tubal surgery. The trial of Dechaud 1998 had a wider range of time from intervention to IVF, varying from one month to 17 months.
Interventions
Seven studies assessed laparoscopic salpingectomy in one of the intervention arms (Dechaud 1998; Dreyer 2016; Fouda 2015; Kontoravdis 2006; Labib 2016; Strandell 1999; Vignarajan 2019). Four trials assessed transvaginal aspiration of hydrosalpingeal fluid (An 2015; Fouda 2011; Fouda 2015; Hammadieh 2008); of these, three reported that the intervention was performed immediately after oocyte retrieval (Fouda 2011; Fouda 2015; Hammadieh 2008), while An 2015 did not allude to the timing of transvaginal aspiration of hydrosalpingeal fluid. Tubal occlusion was performed laparoscopically in three trials (Kontoravdis 2006; Labib 2016; Vignarajan 2019) and hysteroscopically in one (Dreyer 2016), although the Essure® clips used by Dreyer 2016 have since been discontinued by the manufacturer due to safety concerns. Of the analysed trials, seven included a study arm where no tubal surgery was performed (An 2015; Dechaud 1998; Fouda 2011; Hammadieh 2008; Kontoravdis 2006; Moshin 2006; Strandell 1999).
Of the trials assessing salpingectomy, one (Dechaud 1998) performed laparoscopic bilateral salpingectomy regardless of whether tubal disease was unilateral or bilateral; and five (Dreyer 2016; Fouda 2015; Labib 2016; Strandell 1999; Vignarajan 2019) carried out unilateral or bilateral salpingectomy depending on whether unilateral or bilateral hydrosalpinges were present.
All three trials where laparoscopic tubal occlusion was performed used bipolar diathermy applied to the isthmic segment at two separate sites, without draining the hydrosalpinges (Kontoravdis 2006; Labib 2016; Vignarajan 2019). Dreyer 2016 undertook hysteroscopic bilateral tubal occlusion by placing Essure® micro‐inserts into the proximal end of the Fallopian tube with a special delivery system. Moshin 2006 compared salpingectomy with proximal tubal occlusion and no tubal surgery, although the authors did not specify which surgical routes were employed (i.e. laparoscopic or open salpingectomy; and laparoscopic or hysteroscopic occlusion). We have therefore pooled the results from Moshin 2006 exclusively for the meta‐analysis evaluating tubal surgery (all methods) versus no tubal surgery.
No studies analysed salpingostomy as an intervention to treat tubal disease.
Outcomes
Primary outcomes
None of the included studies investigating the main comparison of tubal surgery (all methods) versus no tubal surgery reported on the primary outcome of live birth per woman randomised. For the comparison of tubal occlusion versus laparoscopic salpingectomy, two studies reported on the primary outcome of live birth per woman randomised (Dreyer 2016; Vignarajan 2019). Dreyer 2016 compared hysteroscopic proximal tubal occlusion with laparoscopic salpingectomy, while Vignarajan 2019 compared laparoscopic tubal occlusion with laparoscopic salpingectomy.
Complication rates were reported as pelvic infection rates and complications directly attributable to surgery (e.g. conversion to laparotomy). Five trials reported on rates of pelvic infection (Dreyer 2016; Fouda 2011; Fouda 2015; Hammadieh 2008; Strandell 1999), and three reported on rates of surgical complications (Dreyer 2016; Fouda 2015; Strandell 1999). Of the surgical complications described, Dreyer 2016 reported one case of umbilical incision infection; Fouda 2015 reported zero cases of surgical complications; and Strandell 1999 reported one case of conversion to laparotomy.
Secondary outcomes
All of the included trials reported on clinical pregnancy rates per woman randomised except for Dechaud 1998, where 'pregnancy' was not defined as a viable, clinical or biochemical pregnancy. Nevertheless, Dechaud 1998 reported on ongoing pregnancy rates, and these numbers were extrapolated for the purposes of meta‐analysis for the outcome 'clinical pregnancy rate'.
An 2015 was the only trial reporting on multiple pregnancy rates.
The rates of miscarriage were reported by all trials apart from Labib 2016 and Moshin 2006, while three trials did not report on the rates of ectopic pregnancy (Labib 2016; Moshin 2006; Vignarajan 2019).
All studies reported outcome rate data as absolute frequencies per woman randomised apart from Kontoravdis 2006, whose outcome data were converted from percentages to absolute numbers by the review authors; and Dechaud 1998, where cumulative pregnancy rates were reported for those who underwent more than one ART cycle, although it was possible to extract data per woman randomised for quantitative analysis.
Following the trial by Strandell 1999, a subsequent analysis was published in 2011 with cumulative results from multiple treatment cycles in the original study population. While the 2011 study carried out both an ITT analysis and an analysis per woman treated, 24 out of 77 women who had initially been randomised to no surgical intervention eventually underwent salpingectomy after one or two failed IVF cycles. The previous version of this review considered the follow‐up data to be unsuitable for meta‐analysis, and we are in agreement. For the 2020 update we have therefore maintained the use of data from the original publication in 1999.
The mean number of oocytes and embryos per woman randomised were reported by five trials (Fouda 2011; Fouda 2015; Hammadieh 2008; Kontoravdis 2006; Moshin 2006). Dechaud 1998 and Strandell 1999 reported these rates per cycle and per treated woman, respectively, and we have therefore not included them in our quantitative analysis. We included the mean number of embryos reported by Dreyer 2016 in our meta‐analysis, but the number of oocytes was reported as median ± interquartile range (IQR) and was therefore not included. Vignarajan 2019 reported on the mean number of oocytes only, while An 2015 and Labib 2016 did not refer to the number of oocytes or embryos obtained in their trials.
The included studies and their methodological details are summarised comprehensively in the Characteristics of included studies table.
Author correspondence
We contacted An 2015, Dreyer 2016, Hammadieh 2008, Labib 2016, Lindig 2002, Strandell 1999 and Vignarajan 2019 to obtain and clarify data. To date, we have received responses from all except for An 2015 and Lindig 2002.
Excluded studies
We excluded 13 references for the following reasons.
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Wrong study design (six studies).
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No tubal surgery in either group (two studies).
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Wrong outcomes (two studies).
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Wrong patient population (one study).
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Awaiting classification (two studies).
Risk of bias in included studies
We assessed risk of bias in all included studies as demonstrated in Figure 2 and Figure 3. Detailed information can be found in Characteristics of included studies.
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Allocation
Random sequence generation
Nine studies utilised adequate methods for random sequence generation, such as computer‐generated random number tables, and we therefore deemed them to be at low risk of bias (An 2015; Dreyer 2016; Fouda 2011; Fouda 2015; Hammadieh 2008; Kontoravdis 2006; Labib 2016; Strandell 1999; Vignarajan 2019). Although Dechaud 1998 and Moshin 2006 stated that randomisation occurred, the authors did not specify by which methods, and so we judged these studies to be at unclear risk of bias.
Allocation concealment
Eight studies reported adequate methods for allocation concealment, such as sequentially numbered, sealed opaque envelopes, and we therefore considered them to be at low risk of bias (Dreyer 2016; Fouda 2011; Fouda 2015; Hammadieh 2008; Kontoravdis 2006; Labib 2016; Moshin 2006; Strandell 1999). The remaining three studies provided no relevant details, and so we judged them to be at unclear risk of bias (An 2015; Dechaud 1998; Vignarajan 2019).
Blinding
Blinding of participants and personnel (performance bias)
Vignarajan 2019 was the only study reporting blinding of participants and personnel. We judged it to be at low risk of performance bias. In seven of the included trials, no blinding was performed (An 2015; Dreyer 2016; Fouda 2011; Fouda 2015; Hammadieh 2008; Labib 2016; Strandell 1999) and so we considered these studies to be at high risk of performance bias. No details of blinding were provided for three trials (Dechaud 1998; Kontoravdis 2006; Moshin 2006) and we considered these studies to be at an unclear risk of performance bias.
Blinding of outcome assessment (detection bias)
None of the included studies reported on blinding of outcome assessment, and we therefore judged them all to be at unclear risk of detection bias (An 2015; Dechaud 1998; Dreyer 2016; Fouda 2011; Fouda 2015; Hammadieh 2008; Kontoravdis 2006; Labib 2016; Moshin 2006; Strandell 1999; Vignarajan 2019).
Incomplete outcome data
Three trials reported outcomes on fewer women than the number originally randomised, and we thus judged them to be at high risk of attrition bias (An 2015; Fouda 2011; Kontoravdis 2006). The remaining eight studies analysed all randomised women on an ITT basis (Dechaud 1998; Dreyer 2016; Fouda 2015; Hammadieh 2008; Labib 2016; Moshin 2006; Strandell 1999; Vignarajan 2019) and so we judged them to be at low risk of attrition bias.
Selective reporting
Ten studies reported on a priori outcomes, and we judged these studies to be at low risk of reporting bias (Dechaud 1998; Dreyer 2016; Fouda 2011; Fouda 2015; Hammadieh 2008; Kontoravdis 2006; Labib 2016; Moshin 2006; Strandell 1999; Vignarajan 2019). An 2015 did not include an a priori statement of outcomes to be studied, and so we deemed it to be at unclear risk of bias.
Other potential sources of bias
We deemed seven studies to be at low risk of other bias (Dechaud 1998; Dreyer 2016; Fouda 2011; Fouda 2015; Hammadieh 2008; Kontoravdis 2006; Strandell 1999). We deemed three studies to be at unclear risk of other bias, mostly due to a lack of information on participants' baseline characteristics (An 2015; Labib 2016; Moshin 2006). We considered and one study to be at high risk of other bias due to recruitment ending prematurely (Vignarajan 2019).
Effects of interventions
See: Summary of findings 1 Tubal surgery versus no surgery for tubal disease in women due to undergo in vitro fertilisation; Summary of findings 2 Laparoscopic proximal tubal occlusion versus laparoscopic salpingectomy for tubal disease in women due to undergo in vitro fertilisation; Summary of findings 3 Transvaginal aspiration of hydrosalpingeal fluid versus laparoscopic salpingectomy for tubal disease in women due to undergo in vitro fertilisation
I. Comparison of surgical treatment of hydrosalpinges (all methods) versus no tubal surgery
Primary outcomes
1.0 Live birth rate
None of the included studies reported on the outcome of live birth rate (LBR) for this comparison.
1.1 Surgical complication rate ‐ conversion to laparotomy
We are uncertain of the effect of salpingectomy on the rate of conversion to laparotomy (Peto OR 5.80, 95% CI 0.11 to 303.69; one RCT; n = 204; very low‐quality evidence; Analysis 1.1). Sensitivity analysis based on a random‐effects model showed the same estimates as those obtained with the fixed‐effect model. We found no studies reporting on other types of tubal surgery, such as tubal occlusion or transvaginal aspiration of hydrosalpingeal fluid versus no tubal surgery.
1.2 Surgical complication rate ‐ pelvic infection
We are uncertain of the effect of salpingectomy on the rate of pelvic infection (Peto OR 5.80, 95% CI 0.11 to 303.69; one RCT; n = 204; low‐quality evidence; Analysis 1.2). There were no cases of pelvic infection in the study analysing transvaginal aspiration of hydrosalpingeal fluid versus no intervention and we were thus unable to identify a difference between groups for this comparison (Peto OR not estimable; one RCT; n = 176; Analysis 1.2). Sensitivity analysis based on a random‐effects model showed the same estimates as those obtained with the fixed‐effect model. We found no studies reporting on tubal occlusion versus no tubal surgery for this outcome.
Secondary outcomes
1.3 Clinical pregnancy rate
We found moderate‐quality evidence that salpingectomy probably improves CPR in women with tubal disease compared to no tubal surgery (RR 2.02, 95% CI 1.44 to 2.82; four RCTs; n = 455; I2 = 43%; moderate‐quality evidence; Analysis 1.3; Figure 4). This suggests that with a CPR of approximately 19% (186 per 1000) without tubal surgery, the equivalent CPR with salpingectomy lies between 27% and 52% (268 to 524 per 1000). Additionally, we found that tubal occlusion may increase CPR compared to no tubal surgery (RR 3.21, 95% CI 1.72 to 5.99; two RCTs; n = 209; I2 = 0%; low‐quality evidence; Analysis 1.3; Figure 4). This suggests that with a CPR of approximately 12% (123 per 1000) without tubal surgery, the equivalent CPR with tubal occlusion lies between 21% and 74% (212 to 740 per 1000). Finally, we are uncertain whether transvaginal aspiration of hydrosalpingeal fluid increases CPR compared to no tubal surgery (RR 1.67, 95% CI 1.10 to 2.55; three RCTs; n = 311; I2 = 0%; very low‐quality evidence; Analysis 1.3; Figure 4). This suggests that with a CPR of approximately 18% (178 per 1000) without tubal surgery, the equivalent CPR with transvaginal aspiration of hydrosalpingeal fluid lies between 20% and 45% (196 to 453 per 1000).
Forest plot of comparison: Tubal surgery (all methods) versus no tubal surgery, outcome: 8.1 Clinical pregnancy rate.
1.4 Multiple pregnancy rate
We are uncertain whether transvaginal aspiration of hydrosalpingeal fluid affects the multiple pregnancy rate compared to no tubal surgery (Peto OR 2.15, 95% CI 0.59 to 7.85; one RCT; n = 135; very low‐quality evidence; Analysis 1.4). Similar results are obtained if the multiple pregnancy rate is expressed per clinical pregnancy (Peto OR 2.05, 95% CI 0.45 to 9.42; one RCT; n = 38; very low‐quality evidence; Analysis 1.9).
1.5 Miscarriage rate
Salpingectomy may have little or no difference in miscarriage rate versus no tubal surgery (Peto OR 0.91, 95% CI 0.33 to 2.52; three RCTs; n = 329; I2 = 0%; low‐quality evidence; Analysis 1.5). We are uncertain of the effect of tubal surgery on miscarriage rate with tubal occlusion (Peto OR 0.55, 95% CI 0.04 to 8.43; one RCT; n = 65; very low‐quality evidence; Analysis 1.5) and transvaginal aspiration of hydrosalpingeal fluid (Peto OR 1.27, 95% CI 0.44 to 3.66; three RCTs; n = 311; I2 = 0%; very low‐quality evidence; Analysis 1.5) versus no tubal surgery. Similar results are obtained if the miscarriage rate is expressed per clinical pregnancy for salpingectomy (Peto OR 0.45, 95% CI 0.14 to 1.48; three RCTs; n = 106; I2 = 0%; low‐quality evidence; Analysis 1.10), tubal occlusion (Peto OR 0.04, 95% CI 0.00 to 2.45; one RCT; n = 22; very low‐quality evidence; Analysis 1.10) and transvaginal aspiration of hydrosalpingeal fluid (Peto OR 0.65, 95% CI 0.19 to 2.27; three RCTs; n = 78; I2 = 0%; very low‐quality evidence; Analysis 1.10).
1.6 Ectopic pregnancy rate
Salpingectomy may reduce ectopic pregnancy rate versus no surgery (Peto OR 0.29, 95% CI 0.04 to 2.11; three RCTs; n = 329; I2 = 0%; low‐quality evidence; Analysis 1.6). We are uncertain of the effect of tubal occlusion (Peto OR 3.67, 95% CI 0.04 to 384.48; one RCT; n = 65; very low‐quality evidence; Analysis 1.6) and transvaginal aspiration of hydrosalpingeal fluid (Peto OR 0.59, 95% CI 0.08 to 4.61; three RCTs; n = 311; I2 = 0%; very low‐quality evidence; Analysis 1.6) on ectopic pregnancy rate versus no tubal surgery.
1.7 Mean number of oocytes
Tubal surgery may have no difference in the mean number of oocytes with salpingectomy (MD 0.79, 95% CI ‐0.87 to 2.45; two RCTs; n = 191; I2 = 0%; low‐quality evidence; Analysis 1.7) and tubal occlusion (MD 0.54, 95% CI ‐0.80 to 1.88; two RCTs; n = 244; I2 = 0%; low‐quality evidence; Analysis 1.7) versus no tubal surgery. We are uncertain of the effect of tubal surgery on the mean number of oocytes with transvaginal aspiration of hydrosalpingeal fluid (MD 0.96, 95% CI ‐0.67 to 2.59; two RCTs; n = 176; I2 = 0%; very low‐quality evidence; Analysis 1.7) versus no tubal surgery .
1.8 Mean number of embryos
Salpingectomy may have no difference in the mean number of embryos versus no tubal surgery (MD 0.31, 95% CI ‐1.10 to 1.72; two RCTs; n = 191; I2 = 0%; low‐quality evidence; Analysis 1.8). Additionally, we are uncertain of the effect of tubal surgery on the mean number of embryos with tubal occlusion (MD 0.26, 95% CI ‐1.07 to 1.58; two RCTs; n = 209; I2 = 0%; very low‐quality evidence; Analysis 1.8) and transvaginal aspiration of hydrosalpingeal fluid (MD 0.98, 95% CI ‐0.24 to 2.19; two RCTs; n = 176; I2 = 28%; very low‐quality evidence; Analysis 1.8) versus no tubal surgery.
II. Comparison of proximal tubal occlusion (all methods) versus laparoscopic salpingectomy for hydrosalpinges
Laparoscopic proximal tubal occlusion versus laparoscopic salpingectomy
Primary outcomes
2.1.1 Live birth rate
We are uncertain of the effect of laparoscopic proximal tubal occlusion on LBR compared to laparoscopic salpingectomy (RR 1.21, 95% CI 0.76 to 1.95; one RCT; n = 165; very low‐quality evidence; Analysis 2.1; Figure 5). Sensitivity analysis using OR to express the summary effect measure showed estimates similar to those obtained with RR for laparoscopic proximal tubal occlusion versus laparoscopic salpingectomy (OR 1.31, 95% CI 0.67 to 2.57). No study was at low risk of bias in this comparison, hence the planned sensitivity analysis could not be performed.
Forest plot of comparison: 2 Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, outcome: 2.1 Live birth rate.
2.2.1 Surgical complication rate ‐ wound infection
None of the included studies reported on the effect of laparoscopic proximal tubal occlusion versus laparoscopic salpingectomy on wound infection.
2.3.1 Surgical complication rate ‐ pelvic infection rate
None of the included studies reported on the effect of laparoscopic proximal tubal occlusion versus laparoscopic salpingectomy on pelvic infection rate.
Secondary outcomes
2.4.1 Clinical pregnancy rate
We are uncertain whether CPR is reduced by laparoscopic proximal tubal occlusion (RR 0.81, 95% CI 0.62 to 1.07; three RCTs; n = 347; I2 = 77%; very low‐quality evidence; Analysis 2.4; Figure 6) compared to laparoscopic salpingectomy.
Forest plot of comparison: 2 Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, outcome: 2.4 Clinical pregnancy rate.
2.5.1 Multiple pregnancy rate
None of the included studies reported on the effect of laparoscopic proximal tubal occlusion versus laparoscopic salpingectomy on multiple pregnancy rate.
2.6.1 Miscarriage rate
Laparoscopic proximal tubal occlusion may reduce the miscarriage rate slightly compared to laparoscopic salpingectomy (Peto OR 0.74, 95% CI 0.16 to 3.34; two RCTs; n = 265; I2 = 0%; low‐quality evidence; Analysis 2.6). Similar results are obtained if the miscarriage rate is expressed per clinical pregnancy for laparoscopic tubal occlusion (Peto OR 0.82, 95% CI 0.17 to 3.86; two RCTs; n = 95; I2 = 0%; low‐quality evidence; Analysis 2.11).
2.7.1 Ectopic pregnancy rate
We are uncertain of the effect of laparoscopic proximal tubal occlusion on ectopic pregnancy rate compared to laparoscopic salpingectomy (Peto OR 7.39, 95% CI 0.15 to 372.38; one RCT; n = 100; very low‐quality evidence; Analysis 2.7).
2.8.1 Mean number of oocytes
We are uncertain whether laparoscopic proximal tubal occlusion impacts on the mean number of oocytes compared to laparoscopic salpingectomy (MD 0.4, 95% CI ‐0.67 to 1.48; two RCTs; n = 265; I2 = 17%; very low‐quality evidence; Analysis 2.8).
2.9.1 Mean number of embryos
We are uncertain whether the mean number of embryos is affected by laparoscopic proximal tubal occlusion (MD 0.17, 95% CI ‐1.38 to 1.72; one RCT; n = 100; very low‐quality evidence; Analysis 2.9) compared to laparoscopic salpingectomy.
Hysteroscopic proximal tubal occlusion compared to laparoscopic salpingectomy
One study reported hysteroscopic proximal tubal occlusion versus laparoscopic salpingectomy (Dreyer 2016). The Essure® device used in that study has since been discontinued by the manufacturer.
Primary outcomes
2.1.2 Live birth rate
Hysteroscopic proximal tubal occlusion may reduce LBR compared to laparoscopic salpingectomy (RR 0.46, 95% CI 0.24 to 0.89; one RCT; n = 85; low‐quality evidence; Analysis 2.1; Figure 5). Sensitivity analysis based on a random‐effects model showed the same estimates as those obtained with the fixed‐effect model. Sensitivity analysis using OR to express the summary effect measure showed estimates similar to those obtained with RR for hysteroscopic proximal tubal occlusion versus laparoscopic salpingectomy (OR 0.31, 95% CI 0.12 to 0.81).
2.2.2 Surgical complication rate ‐ wound infection
We are uncertain of the effect of hysteroscopic proximal tubal occlusion on surgical complication rate compared to laparoscopic salpingectomy (Peto OR 0.14, 95% CI 0.00 to 6.98; one RCT; n = 85; very low‐quality evidence; Analysis 2.2). Sensitivity analysis based on a random‐effects model showed the same estimates as those obtained with the fixed‐effect model.
2.3.2 Surgical complication rate ‐ pelvic infection rate
We are uncertain of the effect of hysteroscopic proximal tubal occlusion on pelvic infection rate compared to laparoscopic salpingectomy (Peto OR 7.57, 95% CI 0.15 to 381.46; one RCT; n = 85; very low‐quality evidence; Analysis 2.3). Sensitivity analysis based on a random‐effects model showed the same estimates as those obtained with the fixed‐effect model.
Secondary outcomes
2.4.2 Clinical pregnancy rate
We are uncertain whether CPR is reduced by hysteroscopic proximal tubal occlusion (RR 0.53, 95% CI 0.32 to 0.89; one RCT; n = 85; very low‐quality evidence; Analysis 2.4; Figure 6) compared to laparoscopic salpingectomy.
2.5.2 Multiple pregnancy rate
We are uncertain of the effect of hysteroscopic proximal tubal occlusion on multiple pregnancy rate compared to laparoscopic salpingectomy (Peto OR 0.14, 95% CI 0.00 to 6.98; one RCT; n = 85; very low‐quality evidence; Analysis 2.5). Similar results are obtained if the multiple pregnancy rate is expressed per clinical pregnancy (Peto OR 0.22, 95% CI 0.00 to 13.62; one RCT; n = 38; very low‐quality evidence; Analysis 2.10).
2.6.2 Miscarriage rate
We are uncertain of the effect of hysteroscopic proximal tubal occlusion on the miscarriage rate versus laparoscopic salpingectomy (Peto OR 2.03, 95% CI 0.21 to 20.04; one RCT; n = 85; very low‐quality evidence; Analysis 2.6). Similar results are obtained if the miscarriage rate is expressed per clinical pregnancy for hysteroscopic tubal occlusion (Peto OR 4.59, 95% CI 0.40 to 53.35; one RCT; n = 38; very low‐quality evidence; Analysis 2.11).
2.7.2 Ectopic pregnancy rate
There were no cases of ectopic pregnancy in the included study and we were thus unable to estimate the effect of hysteroscopic proximal tubal occlusion versus laparoscopic salpingectomy (Peto OR not estimable; one RCT; n = 85; Analysis 2.7).
2.8.2 Mean number of oocytes
None of the included studies reported on the effect of hysteroscopic proximal tubal occlusion versus laparoscopic salpingectomy.
2.9.2 Mean number of embryos
We are uncertain whether the mean number of embryos is affected by hysteroscopic proximal tubal occlusion compared to laparoscopic salpingectomy (MD 0.10, 95% CI ‐1.77 to 1.97; one RCT; n = 85; very low‐quality evidence; Analysis 2.9).
III. Comparison of transvaginal aspiration of hydrosalpingeal fluid versus laparoscopic salpingectomy for hydrosalpinges
Primary outcomes
3.0 Live birth rate
None of the included studies reported on the outcome of LBR for this comparison.
3.1 Surgical complication rate
There was insufficient evidence to determine whether transvaginal aspiration of hydrosalpingeal fluid affects the surgical complication rate in comparison to laparoscopic salpingectomy for hydrosalpinges (Peto OR not estimable; one RCT; n = 160; Analysis 3.1). Sensitivity analysis using a random‐effects model was not possible as the OR was not estimable.
Secondary outcomes
3.2 Clinical pregnancy rate
We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on CPR compared to laparoscopic salpingectomy (RR 0.69, 95% CI 0.44 to 1.07; one RCT; n = 160; very low‐quality evidence; Analysis 3.2).
Multiple pregnancy rate
None of the included studies reported on the outcome of multiple pregnancy rate for this comparison.
3.3 Miscarriage rate
We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on miscarriage rate compared to laparoscopic salpingectomy (Peto OR 1.00, 95% CI 0.20 to 5.08; one RCT; n = 160; very low‐quality evidence; Analysis 3.3). Similar results are obtained if the miscarriage rate is expressed per clinical pregnancy (Peto OR 1.53, 95% CI 0.28 to 8.45; one RCT; n = 54; very low‐quality evidence; Analysis 3.7).
3.4 Ectopic pregnancy rate
We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on ectopic pregnancy rate compared to laparoscopic salpingectomy (Peto OR 7.39, 95% CI 0.15 to 372.38; one RCT; n = 160; very low‐quality evidence; Analysis 3.4).
3.5 Mean number of oocytes
We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on the mean number of oocytes compared to laparoscopic salpingectomy (MD 0.34, 95% CI ‐0.85 to 1.53; one RCT; n = 160; very low‐quality evidence; Analysis 3.5).
3.6 Mean number of embryos
We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on the mean number of embryos compared to laparoscopic salpingectomy (MD 0.35, 95% CI ‐0.70 to 1.40; one RCT; n = 160; very low‐quality evidence; Analysis 3.6).
IV. Tubal occlusion (all methods) versus aspiration of hydrosalpingeal fluid
No studies reported on this comparison.
V. Laparoscopic salpingectomy versus any other method of salpingectomy
No studies reported on this comparison.
VI. Laparoscopic tubal occlusion versus hysteroscopic tubal occlusion
No studies reported on this comparison.
Discussion
Summary of main results
This is the third update of a Cochrane Review that aimed to determine whether tubal surgery affects reproductive outcomes in women with tubal disease prior to undergoing ART. The first and second updates were conducted in 2004 and 2010, respectively. In addition to the five RCTs analysed in the previous version of this review (Dechaud 1998; Hammadieh 2008; Kontoravdis 2006; Moshin 2006; Strandell 1999), we included five new published manuscripts (An 2015; Dreyer 2016; Fouda 2011; Fouda 2015; Vignarajan 2019) and one new conference paper (Labib 2016) in the current version.
Tubal surgery versus no tubal surgery
In the previous version of this review, the authors identified no studies reporting on LBR. This remains the case in the current version for the main comparison of tubal surgery versus no surgery in women with tubal disease prior to undergoing ART. Nevertheless, our findings suggest that tubal surgery in the form of salpingectomy probably increases the rate of clinical pregnancy in comparison to no intervention in women undergoing ART. The evidence resulting from trials comparing tubal occlusion to no tubal surgery was of low or very low quality, mainly due to a low number of events (often deriving from a single study) and wide CIs of included studies, although our meta‐analysis indicated that tubal occlusion may also increase CPR in comparison to no intervention. There was no clear evidence of a difference between the groups for surgical complication rate, multiple pregnancy rate, miscarriage rate, ectopic pregnancy rate, mean number of oocytes and mean number of embryos. A subgroup analysis for women younger and older than 40 years old was not possible due to a lack of data.
Proximal tubal occlusion versus laparoscopic salpingectomy
Although Dreyer 2016 and Vignarajan 2019 reported for the first time on LBR in women undergoing tubal occlusion (with hysteroscopy and laparoscopy, respectively) versus laparoscopic salpingectomy, the evidence was judged to be of low and very low quality mainly due to low event rates and wide CIs. Overall, however, the evidence suggests that hysteroscopic proximal tubal occlusion may decrease LBR compared to laparoscopic salpingectomy, although this is not the case for laparoscopic proximal tubal occlusion versus laparoscopic salpingectomy, with no evidence found of a difference in the latter comparison. Furthermore, there was no clear evidence of a difference between the groups for surgical complication rate, CPR, multiple pregnancy rate, miscarriage rate, ectopic pregnancy rate, mean number of oocytes and mean number of embryos. We did not conduct a subgroup analysis based on age due to the paucity of data. It is important to reiterate that the Essure® device used by Dreyer 2016 for hysteroscopic proximal tubal occlusion has now been discontinued and that no other hysteroscopic devices have been studied since in RCTs analysing the treatment of hydrosalpinges prior to IVF/ICSI.
Transvaginal aspiration of hydrosalpinx versus laparoscopic salpingectomy
When transvaginal aspiration of hydrosalpingeal fluid was compared to laparoscopic salpingectomy, the evidence was insufficient to conclude whether or not there was a difference between groups in live birth rate, surgical complication rate, clinical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, mean number of oocytes and mean number of embryos.
Overall completeness and applicability of evidence
In this review, we included 11 studies with 1386 women. The study populations were broadly similar in terms of age and tubal disease. All of the included trials defined tubal disease as the presence of hydrosalpinx in imaging studies or at the time of laparoscopy, with the exception of Dechaud 1998, where tubal diverticula were, in isolation or concurrently to hydrosalpinx, sufficient to make a diagnosis of tubal disease. Given the study populations, the results of this Cochrane Review will be largely applicable to women who have been found to have hydrosalpinges.
Although we were able to include six new trials in the current update, the relatively high number of surgical modalities investigated in the included studies (salpingectomy, tubal occlusion and transvaginal aspiration of hydrosalpingeal fluid) versus no surgical intervention, and the existence of four trials investigating head‐to‐head comparisons between different interventions (Dreyer 2016; Fouda 2015; Labib 2016; Vignarajan 2019), increased the number of analysable comparisons but limited our ability to pool data. Most studies investigating salpingectomy versus no tubal surgery or other intervention clearly stated that salpingectomy was performed laparoscopically, with the exception of Moshin 2006, a conference abstract that did not define the mode of salpingectomy (laparoscopy or laparotomy). In the interest of accuracy, we decided to differentiate between laparoscopic and hysteroscopic tubal occlusion for the purposes of meta‐analysis, given that the rates of adverse events are known to be higher with abdominal surgery.
Despite the known detrimental effect of hydrosalpingeal fluid upon the interface between the implanting embryo and the endometrium, none of the included trials reported on hydrosalpinx size. In addition, none of the included studies commented on the presence or absence of ultrasound‐visible fluid in the endometrial cavity.
Although Hammadieh 2008 alluded to the potential impact of hydrosalpinx re‐accumulation on IVF outcomes following transvaginal aspiration of hydrosalpingeal fluid, the authors did not specify the amount of time elapsed between aspiration and embryo transfer in their trial. Furthermore, of the four trials investigating transvaginal aspiration of hydrosalpingeal fluid (An 2015; Fouda 2011; Fouda 2015; Hammadieh 2008), all reported that transvaginal aspiration was performed immediately after oocyte retrieval, except for An 2015 where no mention of timing was made. Only two of the trials (Fouda 2011 and Fouda 2015) specified the amount of time between oocyte retrieval and embryo transfer (2‐3 days, when it is possible that re‐accumulation of hydrosalpinges would have not yet occurred).
Only two of the included studies reported on the primary outcome of LBR per woman randomised (Dreyer 2016; Vignarajan 2019). Nevertheless, all included studies reported on CPR, and we believe that it is reasonable to postulate that the studied interventions are unlikely to affect second and third trimester pregnancy outcomes. It is clear, however, that there remains a paucity of evidence on live birth rates for all of the interventions studied.
In addition, our findings indicate low rates of complications associated with the studied interventions, although only four studies reported on complication rates (Dreyer 2016; Fouda 2011; Fouda 2015; Hammadieh 2008). This precludes any statistically significant comparisons between groups in the outcomes pertaining to adverse events and may to an extent result from overall low participant numbers. Most of the included studies were underpowered for the analyses of either LBR or CPR, with the exception of Fouda 2011 and Kontoravdis 2006, whose authors clearly stated that a power calculation had been performed and followed. Labib 2016 also stated that a power calculation was performed and followed, although the authors reported results in fewer women than those required by their power calculation. It is unclear whether An 2015 and Moshin 2006 performed a power calculation, while in the remaining six trials a power calculation was performed but not followed, mainly due to slow recruitment (Dechaud 1998; Dreyer 2016; Fouda 2015; Hammadieh 2008; Strandell 1999; Vignarajan 2019). It is therefore likely that the included studies were significantly underpowered to detect differences for surgical complication rates, a much rarer outcome than live birth or clinical pregnancy. In addition, larger and more geographically diverse studies are required to ascertain whether region‐specific causes of tubal disease (e.g. genital tuberculosis and pelvic inflammatory disease leading to significant intraabdominal adhesions) may affect the rates of complications associated with abdominal surgery.
Quality of the evidence
The methodological quality of the included studies varied. Of the 11 included trials, nine were published RCTs (An 2015; Dechaud 1998; Dreyer 2016; Fouda 2011; Fouda 2015; Hammadieh 2008; Kontoravdis 2006; Strandell 1999; Vignarajan 2019) and two were conference abstracts (Labib 2016; Moshin 2006). Correspondence with authors resulted in additional details and data being obtained from Labib 2016, while further data for Moshin 2006 had been provided by the trialists for the previous version of this review. The risk of bias for individual studies is summarised in Figure 2 and Figure 3.
Overall, we identified significant potential for performance bias in the included studies. Vignarajan 2019, where laparoscopic salpingectomy was compared with laparoscopic tubal occlusion, was the only trial clearly stating that blinding of both participants and personnel was undertaken. Six trials stated that participants and personnel were not blinded, mainly due to the nature of the studied intervention (surgery versus no surgery, or abdominal versus hysteroscopic surgery) (An 2015; Dreyer 2016; Fouda 2011; Fouda 2015; Hammadieh 2008; Labib 2016). In the remaining three studies, the authors did not clearly state whether blinding of participants and personnel was performed (Dechaud 1998; Kontoravdis 2006; Moshin 2006).
We also identified significant potential for detection bias in the included trials. None of the included studies specifically stated that there had been blinding of outcome assessors, and we therefore judged them all to be an unclear risk of detection bias (An 2015; Dechaud 1998; Dreyer 2016; Fouda 2011; Fouda 2015; Hammadieh 2008; Kontoravdis 2006; Labib 2016; Moshin 2006; Strandell 1999; Vignarajan 2019
Although patient and personnel blinding may present with challenges in the context of surgical trials, blinding of outcome assessors would have been possible in all of the included studies. Nevertheless, it is likely that many of the measured outcomes would not differ had participants and/or personnel been blinded to the intervention.
The potential for attrition bias was significant in three of the included studies, due to incomplete reporting (An 2015; Fouda 2011; Kontoravdis 2006).
The overall low number of participants and events significantly contributed to downgrading of evidence. As discussed above, power calculations were undertaken but not followed by most of the included trials. Larger, multicentre trials are required to investigate the effect of the different modalities of tubal surgery in women with tubal disease prior to undergoing ART.
We rated the quality of the evidence based on the GRADE criteria. Apart from one moderate‐quality result in one review comparison, the quality of the trials was judged to be low or very low. See summary of findings Table 1, summary of findings Table 2 and summary of findings Table 3.
Potential biases in the review process
In this review, we made every effort to identify all eligible studies. We conducted systematic searches of multiple databases, as well as trial registries, to identify unpublished and ongoing studies. However, it is possible that our searches did not identify all unpublished studies. Data were not available to analyse for our predefined subgroup analyses. We conducted sensitivity analysis where possible, as pre‐specified in our review protocol. We contacted trial authors for missing information where needed. While the majority of authors responded to our correspondence, the requested data were not always available or complete. We were unable to construct a funnel plot due to the small number of included studies. Finally, BWJM was one of the lead investigators in Dreyer 2016 and is also a co‐author in this review.
Agreements and disagreements with other studies or reviews
The previous version of this review was published ten years ago (Johnson 2010). Since then, one new head‐to‐head comparison between salpingectomy and transvaginal aspiration of hydrosalpingeal fluid has been studied by Fouda 2015, while the remaining new trials added to evidence from previously studied comparisons (An 2015; Dreyer 2016; Fouda 2011; Labib 2016; Vignarajan 2019). Additionally, we rated the quality of the evidence in this update based on the GRADE criteria, which were not used in the previous versions of this review.
In this update, the evidence attesting to the effect of salpingectomy versus no surgery was of moderate quality for the outcome of clinical pregnancy, and revealed an effect size similar to that demonstrated in the previous version (Johnson 2010).
The evidence on tubal occlusion versus no tubal surgery was of low or very low quality in this update, although it suggests that, similarly to the results of Johnson 2010, tubal occlusion may increase the clinical pregnancy rate in comparison to no surgery, while there was no evidence of a difference in miscarriage and ectopic pregnancy rate.
In spite of two new RCTs comparing transvaginal aspiration of hydrosalpingeal fluid to no tubal surgery (An 2015; Fouda 2011), the evidence on transvaginal aspiration of hydrosalpingeal fluid is of very low quality for all of the assessed outcomes, in line with the previous version of this review where there was insufficient evidence of an effect.
Crucially, for the first time we included studies that reported on live birth rates (Dreyer 2016; Vignarajan 2019), although the quality of the evidence was judged to be low or very low. Further randomised trials assessing this outcome are required, with larger numbers of participants and, where possible, adequate blinding of participants, personnel and outcome assessors.
Our review did not identify RCTs evaluating salpingostomy as a treatment modality for women with tubal disease prior to undergoing ART. We are therefore unable to add to the systematic review of retrospective observational studies by Chu 2015, which demonstrated a poled live birth rate of 25% in women conceiving naturally following salpingostomy and a pooled ectopic pregnancy rate of 10%.
We also report, for the first time, on the number of oocytes and embryos per woman randomised in the included studies. Our findings did not show evidence of a difference in all of the comparisons analysed.
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Forest plot of comparison: Tubal surgery (all methods) versus no tubal surgery, outcome: 8.1 Clinical pregnancy rate.
Forest plot of comparison: 2 Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, outcome: 2.1 Live birth rate.
Forest plot of comparison: 2 Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, outcome: 2.4 Clinical pregnancy rate.
Comparison 1: Tubal surgery (all methods) vs no tubal surgery, Outcome 1: Surgical complication rate ‐ conversion to laparotomy
Comparison 1: Tubal surgery (all methods) vs no tubal surgery, Outcome 2: Surgical complication rate ‐ pelvic infection
Comparison 1: Tubal surgery (all methods) vs no tubal surgery, Outcome 3: Clinical pregnancy rate
Comparison 1: Tubal surgery (all methods) vs no tubal surgery, Outcome 4: Multiple pregnancy rate
Comparison 1: Tubal surgery (all methods) vs no tubal surgery, Outcome 5: Miscarriage rate
Comparison 1: Tubal surgery (all methods) vs no tubal surgery, Outcome 6: Ectopic pregnancy rate
Comparison 1: Tubal surgery (all methods) vs no tubal surgery, Outcome 7: Mean number of oocytes
Comparison 1: Tubal surgery (all methods) vs no tubal surgery, Outcome 8: Mean number of embryos
Comparison 1: Tubal surgery (all methods) vs no tubal surgery, Outcome 9: Multiple pregnancy rate (per clinical pregnancy)
Comparison 1: Tubal surgery (all methods) vs no tubal surgery, Outcome 10: Miscarriage rate (per clinical pregnancy)
Comparison 2: Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, Outcome 1: Live birth rate
Comparison 2: Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, Outcome 2: Surgical complication rate ‐ wound infection
Comparison 2: Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, Outcome 3: Surgical complication rate ‐ pelvic infection
Comparison 2: Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, Outcome 4: Clinical pregnancy rate
Comparison 2: Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, Outcome 5: Multiple pregnancy rate
Comparison 2: Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, Outcome 6: Miscarriage rate
Comparison 2: Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, Outcome 7: Ectopic pregnancy rate
Comparison 2: Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, Outcome 8: Mean number of oocytes
Comparison 2: Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, Outcome 9: Mean number of embryos
Comparison 2: Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, Outcome 10: Multiple pregnancy rate (per clinical pregnancy)
Comparison 2: Proximal tubal occlusion (all methods) vs laparoscopic salpingectomy, Outcome 11: Miscarriage rate (per clinical pregnancy)
Comparison 3: Transvaginal aspiration of hydrosalpingeal fluid vs laparoscopic salpingectomy, Outcome 1: Surgical complication rate
Comparison 3: Transvaginal aspiration of hydrosalpingeal fluid vs laparoscopic salpingectomy, Outcome 2: Clinical pregnancy rate
Comparison 3: Transvaginal aspiration of hydrosalpingeal fluid vs laparoscopic salpingectomy, Outcome 3: Miscarriage rate
Comparison 3: Transvaginal aspiration of hydrosalpingeal fluid vs laparoscopic salpingectomy, Outcome 4: Ectopic pregnancy rate
Comparison 3: Transvaginal aspiration of hydrosalpingeal fluid vs laparoscopic salpingectomy, Outcome 5: Mean number of oocytes
Comparison 3: Transvaginal aspiration of hydrosalpingeal fluid vs laparoscopic salpingectomy, Outcome 6: Mean number of embryos
Comparison 3: Transvaginal aspiration of hydrosalpingeal fluid vs laparoscopic salpingectomy, Outcome 7: Miscarriage rate (per clinical pregnancy)
| Tubal surgery compared to no surgery for tubal disease in women due to undergo in vitro fertilisation | ||||||
| Patient or population: tubal disease in women due to undergo in vitro fertilisation | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with no tubal surgery | Risk with tubal surgery | |||||
| Live birth rate | No studies reported on this outcome for the main comparison. | |||||
| Surgical complication rate | ||||||
| Salpingectomy (all methods) | 0 per 1,000 | 0 per 1,000 | Peto OR 5.80 | 204 | ⊕⊝⊝⊝ | We are uncertain of the effect of salpingectomy on the rate of conversion to laparotomy. |
| Surgical complication rate | ||||||
| Salpingectomy (all methods) | 0 per 1,000 | 0 per 1,000 (0 to 0) | Peto OR 5.80 (0.11 to 303.69) | 204 (1 RCT) | ⊕⊝⊝⊝ | We are uncertain of the effect of salpingectomy on the rate of pelvic infection. |
| Transvaginal aspiration of hydrosalpingeal fluid | 0 per 1,000 | 0 per 1,000 (0 to 0) | Not estimable | 176 (1 RCT) | ‐ | There were insufficient data to estimate differences between groups. |
| Clinical pregnancy rate | ||||||
| Salpingectomy (all methods) | 186 per 1,000 | 376 per 1,000 | RR 2.02 | 455 | ⊕⊕⊕⊝ | Salpingectomy probably increases clinical pregnancy rate. |
| Tubal occlusion (all methods) | 123 per 1,000 | 396 per 1,000 | RR 3.21 | 209 | ⊕⊕⊝⊝ | Tubal occlusion may increase clinical pregnancy rate. |
| Transvaginal aspiration of hydrosalpingeal fluid | 178 per 1,000 | 297 per 1,000 | RR 1.67 | 311 | ⊕⊝⊝⊝ | We are uncertain whether transvaginal aspiration of hydrosalpingeal fluid increases clinical pregnancy rate. |
| Miscarriage rate | ||||||
| Salpingectomy (all methods) | 53 per 1,000 | 48 per 1,000 | Peto OR 0.91 | 329 | ⊕⊕⊝⊝ | Salpingectomy may have little or no difference in miscarriage rate. |
| Tubal occlusion (all methods) | 67 per 1,000 | 40 per 1,000 | Peto OR 0.55 | 65 | ⊕⊝⊝⊝ | We are uncertain of the effect of tubal occlusion on miscarriage rate. |
| Transvaginal aspiration of hydrosalpingeal fluid | 44 per 1,000 | 56 per 1,000 | Peto OR 1.27 | 311 | ⊕⊝⊝⊝ | We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on miscarriage rate. |
| Ectopic pregnancy rate | ||||||
| Salpingectomy (all methods) | 23 per 1,000 | 8 per 1,000 | Peto OR 0.29 | 329 | ⊕⊕⊝⊝ | Salpingectomy may reduce ectopic pregnancy rate. |
| Tubal occlusion (all methods) | 0 per 1,000 | 0 per 1,000 | Peto OR 3.67 | 65 | ⊕⊝⊝⊝ | We are uncertain of the effect of tubal occlusion on miscarriage rate. |
| Transvaginal aspiration of hydrosalpingeal fluid | 15 per 1,000 | 10 per 1,000 | Peto OR 0.59 | 311 | ⊕⊝⊝⊝ | We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on ectopic pregnancy rate. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded one level for imprecision: wide confidence intervals. bDowngraded one level for imprecision: low number of participants. cDowngraded one level for risk of bias: at least one study with two domains at high risk of bias. dDowngraded one level for imprecision: single small study. | ||||||
| Laparoscopic proximal tubal occlusion versus laparoscopic salpingectomy for tubal disease in women due to undergo in vitro fertilisation | ||||||
| Patient or population: tubal disease in women due to undergo in vitro fertilisation | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with laparoscopic salpingectomy | Risk with proximal tubal occlusion | |||||
| Live birth rate | ||||||
| Laparoscopic proximal tubal occlusion vs laparoscopic salpingectomy | 268 per 1,000 | 325 per 1,000 | RR 1.21 | 165 | ⊕⊝⊝⊝ | We are uncertain of the effect of laparoscopic proximal tubal occlusion on live birth rate compared to laparoscopic salpingectomy. |
| Surgical complication rate | No study reported on this outcome for laparoscopic proximal tubal occlusion. | |||||
| Surgical complication rate | No study reported on this outcome for laparoscopic proximal tubal occlusion. | |||||
| Clinical pregnancy rate | ||||||
| Laparoscopic proximal tubal occlusion vs laparoscopic salpingectomy | 410 per 1,000 | 332 per 1,000 | RR 0.81 | 347 | ⊕⊝⊝⊝ | We are uncertain of the effect of laparoscopic proximal tubal occlusion on clinical pregnancy rate compared to laparoscopic salpingectomy. |
| Miscarriage rate | ||||||
| Laparoscopic proximal tubal occlusion vs laparoscopic salpingectomy | 30 per 1,000 | 23 per 1,000 | Peto OR 0.74 | 265 | ⊕⊕⊝⊝ | Laparoscopic proximal tubal occlusion may reduce miscarriage rate slightly compared to laparoscopic salpingectomy. |
| Ectopic pregnancy rate | ||||||
| Laparoscopic proximal tubal occlusion vs laparoscopic salpingectomy | 0 per 1,000 | 0 per 1,000 | Peto OR 7.39 | 100 | ⊕⊝⊝⊝ | We are uncertain of the effect of laparoscopic proximal tubal occlusion on ectopic pregnancy rate compared to laparoscopic salpingectomy. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded one level for imprecision: low number of participants. bDowngraded one level for imprecision: single small study. cDowngraded one level for imprecision: wide confidence intervals. dDowngraded one level for inconsistency: high degree of heterogeneity. | ||||||
| Transvaginal aspiration of hydrosalpinx versus laparoscopic salpingectomy for tubal disease in women due to undergo in vitro fertilisation | ||||||
| Patient or population: tubal disease in women due to undergo in vitro fertilisation | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with laparoscopic salpingectomy | Risk with transvaginal aspiration of hydrosalpingeal fluid | |||||
| Live birth rate | No studies reported on this outcome. | |||||
| Surgical complication rate | 0 per 1,000 | 0 per 1,000 | not estimable | 160 | ‐ | There were insufficient data to estimate differences between groups. |
| Clinical pregnancy rate | 400 per 1,000 | 276 per 1,000 | RR 0.69 (0.44 to 1.07) | 160 | ⊕⊝⊝⊝ | We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on clinical pregnancy rate compared to laparoscopic salpingectomy. |
| Miscarriage rate | 38 per 1,000 | 38 per 1,000 | Peto OR 1.00 (0.20 to 5.08) | 160 | ⊕⊝⊝⊝ | We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on miscarriage rate compared to laparoscopic salpingectomy. |
| Ectopic pregnancy rate | 0 per 1,000 | 0 per 1,000 | Peto OR 7.39 (0.15 to 372.38) | 160 | ⊕⊝⊝⊝ | We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid on ectopic pregnancy rate compared to laparoscopic salpingectomy. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded one level for imprecision: low number of participants. bDowngraded one level for imprecision: single small study. cDowngraded one level for imprecision: wide confidence intervals. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Surgical complication rate ‐ conversion to laparotomy Show forest plot | 1 | 204 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 5.80 [0.11, 303.69] |
| 1.1.1 Salpingectomy (all methods) vs no tubal surgery | 1 | 204 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 5.80 [0.11, 303.69] |
| 1.2 Surgical complication rate ‐ pelvic infection Show forest plot | 3 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 1.2.1 Salpingectomy (all methods) vs no tubal surgery | 1 | 204 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 5.80 [0.11, 303.69] |
| 1.2.2 Transvaginal aspiration of hydrosalpingeal fluid vs no tubal surgery | 2 | 176 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Not estimable |
| 1.3 Clinical pregnancy rate Show forest plot | 7 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.3.1 Salpingectomy (all methods) vs no tubal surgery | 4 | 455 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.02 [1.44, 2.82] |
| 1.3.2 Tubal occlusion (all methods) vs no tubal surgery | 2 | 209 | Risk Ratio (M‐H, Fixed, 95% CI) | 3.21 [1.72, 5.99] |
| 1.3.3 Transvaginal aspiration of hydrosalpingeal fluid vs no tubal surgery | 3 | 311 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.67 [1.10, 2.55] |
| 1.4 Multiple pregnancy rate Show forest plot | 1 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 1.4.1 Transvaginal aspiration of hydrosalpingeal fluid vs no tubal surgery | 1 | 135 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 2.15 [0.59, 7.85] |
| 1.5 Miscarriage rate Show forest plot | 6 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 1.5.1 Salpingectomy (all methods) vs no tubal surgery | 3 | 329 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.91 [0.33, 2.52] |
| 1.5.2 Tubal occlusion (all methods) vs no tubal surgery | 1 | 65 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.55 [0.04, 8.43] |
| 1.5.3 Transvaginal aspiration of hydrosalpingeal fluid vs no tubal surgery | 3 | 311 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 1.27 [0.44, 3.66] |
| 1.6 Ectopic pregnancy rate Show forest plot | 6 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 1.6.1 Salpingectomy (all methods) vs no tubal surgery | 3 | 329 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.29 [0.04, 2.11] |
| 1.6.2 Tubal occlusion (all methods) vs no tubal surgery | 1 | 65 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 3.67 [0.04, 384.48] |
| 1.6.3 Transvaginal aspiration of hydrosalpingeal fluid vs no tubal surgery | 3 | 311 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.59 [0.08, 4.61] |
| 1.7 Mean number of oocytes Show forest plot | 4 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.7.1 Salpingectomy (all methods) vs no tubal surgery | 2 | 191 | Mean Difference (IV, Fixed, 95% CI) | 0.79 [‐0.87, 2.45] |
| 1.7.2 Tubal occlusion (all methods) vs no tubal surgery | 2 | 244 | Mean Difference (IV, Fixed, 95% CI) | 0.54 [‐0.80, 1.88] |
| 1.7.3 Transvaginal aspiration of hydrosalpingeal fluid vs no tubal surgery | 2 | 176 | Mean Difference (IV, Fixed, 95% CI) | 0.96 [‐0.67, 2.59] |
| 1.8 Mean number of embryos Show forest plot | 4 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.8.1 Salpingectomy (all methods) vs no tubal surgery | 2 | 191 | Mean Difference (IV, Fixed, 95% CI) | 0.31 [‐1.10, 1.72] |
| 1.8.2 Tubal occlusion (all methods) vs no tubal surgery | 2 | 209 | Mean Difference (IV, Fixed, 95% CI) | 0.26 [‐1.07, 1.58] |
| 1.8.3 Transvaginal aspiration of hydrosalpingeal fluid vs no tubal surgery | 2 | 176 | Mean Difference (IV, Fixed, 95% CI) | 0.98 [‐0.24, 2.19] |
| 1.9 Multiple pregnancy rate (per clinical pregnancy) Show forest plot | 1 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 1.9.1 Transvaginal aspiration of hydrosalpingeal fluid vs no tubal surgery | 1 | 38 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 2.05 [0.45, 9.42] |
| 1.10 Miscarriage rate (per clinical pregnancy) Show forest plot | 6 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 1.10.1 Salpingectomy (all methods) vs no tubal surgery | 3 | 106 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.45 [0.14, 1.48] |
| 1.10.2 Tubal occlusion (all methods) vs no tubal surgery | 1 | 22 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.04 [0.00, 2.45] |
| 1.10.3 Transvaginal aspiration of hydrosalpingeal fluid vs no tubal surgery | 3 | 78 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.65 [0.19, 2.27] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Live birth rate Show forest plot | 2 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 2.1.1 Proximal tubal occlusion (laparoscopy) vs laparoscopic salpingectomy | 1 | 165 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.21 [0.76, 1.95] |
| 2.1.2 Proximal tubal occlusion (hysteroscopy) vs laparoscopic salpingectomy | 1 | 85 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.46 [0.24, 0.89] |
| 2.2 Surgical complication rate ‐ wound infection Show forest plot | 1 | 85 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.14 [0.00, 6.98] |
| 2.2.1 Proximal tubal occlusion (hysteroscopy) vs laparoscopic salpingectomy | 1 | 85 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.14 [0.00, 6.98] |
| 2.3 Surgical complication rate ‐ pelvic infection Show forest plot | 1 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 2.3.1 Proximal tubal occlusion (hysteroscopy) vs laparoscopic salpingectomy | 1 | 85 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 7.57 [0.15, 381.46] |
| 2.4 Clinical pregnancy rate Show forest plot | 4 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 2.4.1 Proximal tubal occlusion (laparoscopy) vs laparoscopic salpingectomy | 3 | 347 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.81 [0.62, 1.07] |
| 2.4.2 Proximal tubal occlusion (hysteroscopy) vs laparoscopic salpingectomy | 1 | 85 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.53 [0.32, 0.89] |
| 2.5 Multiple pregnancy rate Show forest plot | 1 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 2.5.1 Proximal tubal occlusion (hysteroscopy) vs laparoscopic salpingectomy | 1 | 85 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.14 [0.00, 6.98] |
| 2.6 Miscarriage rate Show forest plot | 3 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 2.6.1 Proximal tubal occlusion (laparoscopy) vs laparoscopic salpingectomy | 2 | 265 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.74 [0.16, 3.34] |
| 2.6.2 Proximal tubal occlusion (hysteroscopy) vs laparoscopic salpingectomy | 1 | 85 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 2.03 [0.21, 20.04] |
| 2.7 Ectopic pregnancy rate Show forest plot | 2 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 2.7.1 Proximal tubal occlusion (laparoscopy) vs laparoscopic salpingectomy | 1 | 100 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 7.39 [0.15, 372.38] |
| 2.7.2 Proximal tubal occlusion (hysteroscopy) vs laparoscopic salpingectomy | 1 | 85 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Not estimable |
| 2.8 Mean number of oocytes Show forest plot | 2 | 265 | Mean Difference (IV, Fixed, 95% CI) | 0.40 [‐0.67, 1.48] |
| 2.8.1 Proximal tubal occlusion (laparoscopy) vs laparoscopic salpingectomy | 2 | 265 | Mean Difference (IV, Fixed, 95% CI) | 0.40 [‐0.67, 1.48] |
| 2.9 Mean number of embryos Show forest plot | 2 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 2.9.1 Proximal tubal occlusion (laparoscopy) vs laparoscopic salpingectomy | 1 | 100 | Mean Difference (IV, Fixed, 95% CI) | 0.17 [‐1.38, 1.72] |
| 2.9.2 Proximal tubal occlusion (hysteroscopy) vs laparoscopic salpingectomy | 1 | 85 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐1.77, 1.97] |
| 2.10 Multiple pregnancy rate (per clinical pregnancy) Show forest plot | 1 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 2.10.1 Proximal tubal occlusion (hysteroscopy) vs laparoscopic salpingectomy | 1 | 38 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.22 [0.00, 13.62] |
| 2.11 Miscarriage rate (per clinical pregnancy) Show forest plot | 3 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 2.11.1 Proximal tubal occlusion (laparoscopy) vs laparoscopic salpingectomy | 2 | 95 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.82 [0.17, 3.86] |
| 2.11.2 Proximal tubal occlusion (hysteroscopy) vs laparoscopic salpingectomy | 1 | 38 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 4.59 [0.40, 53.35] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 Surgical complication rate Show forest plot | 1 | 160 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Not estimable |
| 3.2 Clinical pregnancy rate Show forest plot | 1 | 160 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.44, 1.07] |
| 3.3 Miscarriage rate Show forest plot | 1 | 160 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 1.00 [0.20, 5.08] |
| 3.4 Ectopic pregnancy rate Show forest plot | 1 | 160 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 7.39 [0.15, 372.38] |
| 3.5 Mean number of oocytes Show forest plot | 1 | 160 | Mean Difference (IV, Fixed, 95% CI) | 0.34 [‐0.85, 1.53] |
| 3.6 Mean number of embryos Show forest plot | 1 | 160 | Mean Difference (IV, Fixed, 95% CI) | 0.35 [‐0.70, 1.40] |
| 3.7 Miscarriage rate (per clinical pregnancy) Show forest plot | 1 | 54 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 1.53 [0.28, 8.45] |
