Abstract
Background
Fibroids are the most common benign tumours of the female genital tract and are associated with numerous clinical problems including a possible negative impact on fertility. In women requesting preservation of fertility, fibroids can be surgically removed (myomectomy) by laparotomy, laparoscopically or hysteroscopically depending on the size, site and type of fibroid. Myomectomy is however a procedure that is not without risk and can result in serious complications. It is therefore essential to determine whether such a procedure can result in an improvement in fertility and, if so, to then determine the ideal surgical approach.
Objectives
To examine the effect of myomectomy on fertility outcomes and to compare different surgical approaches.
Search methods
We searched the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Epistemonikos database, World Health Organization (WHO) International Clinical Trials Registry Platform search portal, Database of Abstracts of Reviews of Effects (DARE), LILACS, conference abstracts on the ISI Web of Knowledge, OpenSigle for grey literature from Europe, and reference list of relevant papers. The final search was in February 2019.
Selection criteria
Randomised controlled trials (RCTs) examining the effect of myomectomy compared to no intervention or where different surgical approaches are compared regarding the effect on fertility outcomes in a group of infertile women suffering from uterine fibroids.
Data collection and analysis
Data collection and analysis were conducted in accordance with the procedure suggested in the Cochrane Handbook for Systematic Reviews of Interventions.
Main results
This review included four RCTs with 442 participants. The evidence was very low‐quality with the main limitations being due to serious imprecision, inconsistency and indirectness.
Myomectomy versus no intervention
One study examined the effect of myomectomy compared to no intervention on reproductive outcomes. We are uncertain whether myomectomy improves clinical pregnancy rate for intramural (odds ratio (OR) 1.88, 95% confidence interval (CI) 0.57 to 6.14; 45 participants; one study; very low‐quality evidence), submucous (OR 2.04, 95% CI 0.62 to 6.66; 52 participants; one study; very low‐quality evidence), intramural/subserous (OR 2.00, 95% CI 0.40 to 10.09; 31 participants; one study; very low‐quality evidence) or intramural/submucous fibroids (OR 3.24, 95% CI 0.72 to 14.57; 42 participants; one study; very low‐quality evidence). Similarly, we are uncertain whether myomectomy reduces miscarriage rate for intramural fibroids (OR 1.33, 95% CI 0.26 to 6.78; 45 participants; one study; very low‐quality evidence), submucous fibroids (OR 1.27, 95% CI 0.27 to 5.97; 52 participants; one study; very low‐quality evidence), intramural/subserous fibroids (OR 0.80, 95% CI 0.10 to 6.54; 31 participants; one study; very low‐quality evidence) or intramural/submucous fibroids (OR 2.00, 95% CI 0.32 to 12.33; 42 participants; one study; very low‐quality evidence). This study did not report on live birth, preterm delivery, ongoing pregnancy or caesarean section rate.
Laparoscopic myomectomy versus myomectomy by laparotomy or mini‐laparotomy
Two studies compared laparoscopic myomectomy to myomectomy at laparotomy or mini‐laparotomy. We are uncertain whether laparoscopic myomectomy compared to laparotomy or mini‐laparotomy improves live birth rate (OR 0.80, 95% CI 0.42 to 1.50; 177 participants; two studies; I2 = 0%; very low‐quality evidence), preterm delivery rate (OR 0.70, 95% CI 0.11 to 4.29; participants = 177; two studies; I2 = 0%, very low‐quality evidence), clinical pregnancy rate (OR 0.96, 95% CI 0.52 to 1.78; 177 participants; two studies; I2 = 0%, very low‐quality evidence), ongoing pregnancy rate (OR 1.61, 95% CI 0.26 to 10.04; 115 participants; one study; very low‐quality evidence), miscarriage rate (OR 1.25, 95% CI 0.40 to 3.89; participants = 177; two studies; I2 = 0%, very low‐quality evidence), or caesarean section rate (OR 0.69, 95% CI 0.34 to 1.39; participants = 177; two studies; I2 = 21%, very low‐quality evidence).
Monopolar resectoscope versus bipolar resectoscope
One study evaluated the use of two electrosurgical systems during hysteroscopic myomectomy. We are uncertain whether bipolar resectoscope use compared to monopolar resectoscope use improves live birth/ongoing pregnancy rate (OR 0.86, 95% CI 0.30 to 2.50; 68 participants; one study, very low‐quality evidence), clinical pregnancy rate (OR 0.88, 95% CI 0.33 to 2.36; 68 participants; one study; very low‐quality evidence), or miscarriage rate (OR 1.00, 95% CI 0.19 to 5.34; participants = 68; one study; very low‐quality evidence). This study did not report on preterm delivery or caesarean section rate.
Authors' conclusions
There is limited evidence to determine the role of myomectomy for infertility in women with fibroids as only one trial compared myomectomy with no myomectomy. If the decision is made to have a myomectomy, the current evidence does not indicate a superior method (laparoscopy, laparotomy or different electrosurgical systems) to improve rates of live birth, preterm delivery, clinical pregnancy, ongoing pregnancy, miscarriage, or caesarean section. Furthermore, the existing evidence needs to be viewed with caution due to the small number of events, minimal number of studies and very low‐quality evidence.
Plain language summary
Does surgical removal of fibroids improve fertility outcomes?
Review question
Cochrane authors reviewed the evidence about the effect on fertility with the surgical removal of fibroids in infertile women.
Background
Fibroids are the most common benign tumours of the female genital tract and commonly affect women of reproductive age. Fibroids occur in different parts of the womb and can vary in size and shape. Fibroids can lead to a variety of symptoms including heavy periods, pain, difficulty to conceive, or problems with pregnancy such as miscarriage and premature labour. In women wishing to preserve their fertility, it is possible to remove the fibroid while preserving the womb, an operation known as myomectomy. This procedure can be performed by laparotomy (open abdominal surgery), laparoscopic surgery (a key‐hole through the abdomen) or hysteroscopic surgery (a key‐hole through the neck of the womb) depending on the site and size of the fibroid. This review aimed to answer two questions. Firstly, whether myomectomy led to an improvement in fertility; and secondly, if the procedure is beneficial, what is the ideal surgical approach?
Study characteristics
This review included four studies with 442 participants. One study compared myomectomy to no treatment. The remaining three studies compared different surgical methods of performing a myomectomy. The evidence is current to February 2019.
Key results
One study examined the effect of myomectomy compared to no treatment. Results found insufficient evidence to determine a difference between treatment options for clinical pregnancy rate or miscarriage rate. This study did not report on live birth, preterm delivery, ongoing pregnancy or caesarean section rate. Regarding the best surgical approach, three studies were identified. Two studies compared myomectomy by mini‐laparotomy or laparotomy to laparoscopic myomectomy and found insufficient evidence to determine a difference for live birth, preterm delivery, clinical pregnancy, miscarriage, caesarean section and ongoing pregnancy rate. The third study compared use of different surgical equipment during hysteroscopic myomectomy and found insufficient evidence to determine a difference for live birth/ongoing pregnancy rate, clinical pregnancy rate and miscarriage rate. This study did not report on caesarean section or preterm delivery rate. It is clear that more studies are needed before a consensus can be reached on the role of myomectomy for infertility.
Quality of evidence
The evidence was very low quality. There are some concerns regarding how the data were analysed and therefore the evidence cannot be considered to be conclusive until further studies are available.
Summary of findings
Background
Description of the condition
Fibroids (also known as leiomyomas) are the most common benign tumours of the female genital tract and occur in about 20% to 50% of women (Yoshino 2010). They have been linked to many gynaecological problems including heavy menstrual bleeding and infertility. Fibroids are estimated to be the sole cause of infertility in less than 3% of cases (Farquhar 2009) and the mechanisms by which they can affect fertility vary depending on the type of fibroid. These mechanisms include causing possible anatomical changes affecting the cervix, uterus, tubes and ovaries, or causing a local endometrial inflammatory reaction leading to impaired endometrial receptivity, sperm transport or myometrial contractility (Inagaki 2003; Kroon 2011; Yoshino 2010; Yoshino 2012).
The evidence regarding the effect of fibroids on fertility depends mainly on the type of fibroid (submucous (SM), intramural (IM) or subserous (SS)), and this has been extensively reviewed in several studies (Somigliana 2007; Klatsky 2008; Pritts 2009; Sunkara 2010; Metwally 2011). Current evidence suggests the presence of an SM fibroid is detrimental for fertility, while SS fibroids seem to have little effect. The evidence regarding IM fibroids is less conclusive and there is no clear consensus regarding the effect of these fibroids on fertility outcomes.
Description of the intervention
Myomectomy is the procedure by which fibroids are removed whilst conserving the uterus. This procedure has been reported as far back as 1845, where the removal of an SS fibroid was described in the American Journal of Medical Sciences for a woman thought to have an ovarian cyst. The procedure was successful despite being performed in the pre‐anaesthetic era through a midline incision. It was not until the early 20th century that myomectomy by laparotomy gained popularity, largely due to the haemostatic and surgical techniques developed by Victor Bonney (Chamberlain 2003). In the late 1970s, laparoscopic myomectomy was first described for SS fibroids, which extended to IM fibroids by the early 1990s (Dubuisso 2000). Since 2015, the routine use of laparoscopic myomectomy has fallen, following case reports of iatrogenic spreading of non‐benign leiomyomas within the peritoneum during morcellation (permitting fibroid extraction from the abdomen through small incisions)(Hall 2015). Consequently, alternative techniques are favoured.
SM fibroids are currently predominantly managed using hysteroscopic resection techniques. Hysteroscopic myomectomy was pioneered largely as a consequence of development of the urological resectoscope. By the mid 1980s, instrument modifications led to the development of the gynaecological resectoscope with a 0° optical lens, a continuous flow irrigation system using 1.5% glycine and monopolar energy (Hallez 1995). Today, hysteroscopic myomectomy can also be performed by a bipolar resectoscope. Fundamentally, there are several important differences in electrosurgical systems. Use of a bipolar resectoscope allows the use of an electrolytic uterine distension medium such as normal saline (Sardo 2008; Metwally 2015). This medium, as opposed to the non‐conducting distension medium used in monopolar procedures, can be used without the risk of adverse effects such as fluid overload, hyponatraemia and cerebral oedema (Emanuel 1997). Secondly, with the closed circuit seen in a bipolar electrosurgical system, the risk of spread of thermal energy is minimised, allowing a more precise tissue effect being exerted (Litta 2014b).
How the intervention might work
For some types of fibroids, such as SM fibroids where a clear negative effect on fertility has been demonstrated, myomectomy may improve fertility by restoring the normal anatomy of the uterus. With other types of fibroids, such as IM fibroids, the effect on fertility and therefore the effect of intervention on fertility remains less clear. It is possible that myomectomy may reverse some of the other associated abnormalities, such as the local endometrial inflammatory reaction, impaired gamete interaction and abnormal myometrial contractility, which could lead to improvement in implantation.
Why it is important to do this review
A societal shift in reproductive behaviour has meant women are more frequently delaying pregnancy until later in reproductive years. In 2017, 55% of mothers were aged 30 years and over, compared to 43% in 1997 (Office for National Statistics 2019). The delayed timing of pregnancy coincides with the peak incidence and diagnosis of fibroids. It is therefore predicted that by 2050, the number of myomectomies performed will increase by 31% (Wechter 2011). The majority of evidence reports an improvement in pregnancy rates (ranging from 10% to 77%) after myomectomy. This evidence is derived from case series rather than randomised controlled trials (Farquhar 2009). In addition, myomectomy carries inherent risks that may be detrimental to fertility. Myomectomy can reduce chances of conception due to peritoneal and intrauterine adhesions. Furthermore, the procedure prolongs time to conception due to surgical recovery. Additionally, laparoscopic myomectomy and myomectomy by laparotomy or mini‐laparotomy increases the risk of scar rupture in a future pregnancy. It is therefore essential to determine the relationship between myomectomy and reproductive outcomes based on high‐quality randomised controlled studies. Furthermore, considering the heterogenous nature of fibroids, it is essential that clinicians have clear guidance on when intervention is appropriate based on type of fibroid (SM, IM, SS).
Objectives
To examine the effect of myomectomy on fertility outcomes and to compare different surgical approaches.
Methods
Criteria for considering studies for this review
Types of studies
Only randomised controlled trials (RCTs) examining the effect of myomectomy compared to no treatment or a different surgical method were eligible for inclusion. Cross‐over trials were not applicable in this context. Studies examining the effect of fibroid embolisation were not included as these are included in a separate review (Gupta 2014).
Types of participants
Women with uterine fibroids seeking infertility treatment, with or without symptoms.
Types of interventions
Surgical removal of fibroids by myomectomy at laparotomy, laparoscopy or hysteroscopy compared to no intervention or a different surgical method.
Types of outcome measures
Primary outcomes
1. Live birth rate (LBR), defined as the number of live births per woman
2. Preterm delivery rate (PDR) per woman
Secondary outcomes
3. Clinical pregnancy rate (CPR) per woman
4. Ongoing pregnancy rate (OPR) per woman, defined as a pregnancy progressing beyond 12 weeks of gestation
5. Miscarriage rate (MR) per woman
6. Caesarean section rate (CSR) per woman
Search methods for identification of studies
Electronic searches
The following databases were searched
The Cochrane Gynaecology and Fertility Group (CGF) Specialised Register of Controlled Trials; PROCITE platform, searched 26 February 2019 (Appendix 1)
CENTRAL via The Cochrane Register of Studies Online (CRSO); web platform, searched 26 February 2019 (Appendix 2)
MEDLINE; Ovid platform, searched from 1946 to 26 February 2019 (Appendix 3)
Embase Ovid platform, searched from 1980 to 26 February 2019 (Appendix 4)
PsycINFO Ovid platform, searched from 1806 to 26 February 2019 (Appendix 5)
CINAHL; (Cumulative Index to Nursing and Allied Health Literature), EBSCO platform, searched from 1961 to 26 February 2019 (Appendix 6)
The MEDLINE search was combined with the Cochrane highly sensitive search strategy for identifying randomised trials, which appears in the Cochrane Handbook of Systematic Reviews of Interventions Version 5.1.0 (Chapter 6, 6.4.11) (Higgins 2011). The Embase, PsychINFO and CINAHL search were combined with trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN) (https://www.sign.ac.uk/search‐filters.html). There was no language restriction in these searches.
Other electronic sources of trials included (January 2012 to April 2019).
Epistemonikos database (https://www.epistemonikos.org/en)
World Health Organization International Clinical Trials Registry Platform search portal (http://www.who.int/trialsearch/Default.aspx)
LILACS database, which provides a source of trials from the Portuguese and Spanish speaking world (http://regional.bvsalud.org/php/index.php?lang=en)
PubMed and Google Scholar (for recent trials not yet indexed in major databases)
Grey literature (http://www.opengrey.eu/)
The following journals were also searched electronically (January 2012 to April 2019).
Fertility and Sterility
Human Reproduction
Obstetrics and Gynecology
American Journal of Obstetrics and Gynecology
British Journal of Obstetrics and Gynaecology
European Journal of Obstetrics, Gynecology, and Reproductive Biology
Gynaecological Endoscopy
Surgical Endoscopy
Searching other resources
We handsearched reference lists of articles retrieved by the search and contacted experts in the field to obtain additional data. Previously excluded studies in this review were reassessed for eligibility. We also handsearched relevant journals and conference abstracts that are not covered in the CGF register, in liaison with the Information Specialist.
Data collection and analysis
Selection of studies
Titles and abstracts were screened independently by two review authors (GR and MM) to exclude studies that were clearly irrelevant. Full texts of potentially eligible studies were then retrieved and examined independently by GR and MM for compliance with the predefined inclusion criteria. We corresponded with study investigators as required to clarify study eligibility. Any disagreements regarding eligibility were resolved at a subsequent meeting. The selection process was documented with a PRISMA flow chart.
Data extraction and management
Two review authors (GR and MM) independently extracted data using a data extraction form designed and pilot‐tested by the review authors. Study characteristics and outcome data were extracted (see data extraction table for details, Appendix 7). When studies had multiple publications, the review authors collated all reports of the same study under a single study ID with multiple references. Where data were missing or unclear, we corresponded with study investigators for further data on methods and/or results, as required.
Assessment of risk of bias in included studies
Two review authors (GR and MM) independently assessed included studies for risk of bias using the Cochrane 'Risk of bias' assessment tool (Cochrane Handbook of Systematic Reviews of Interventions Version 5.1.0) (Higgins 2011). Seven domains were assessed: selection bias (random sequence generation), selection bias (allocation concealment), attrition bias (incomplete outcome data), reporting bias (selective reporting), performance bias (blinding of participants and personnel), detection bias (blinding of outcome assessors), and other biases (other problems that could put a trial at high risk of bias). Judgements were assigned as recommended in the Cochrane Handbook Section 8.5 (Higgins 2011). Any disagreements were resolved by consensus. We described all the judgements fully and presented the conclusions in the 'Risk of bias' tables.
Measures of treatment effect
We performed statistical analysis in accordance with the guidelines developed by the Cochrane Gynaecology and Fertility group. Dichotomous data were retrieved and analysed using the Mantel‐Haenszel odds ratios (ORs) with 95% confidence intervals (CIs).
Unit of analysis issues
The primary analysis is presented as per woman randomised. If relevant, rate per clinical pregnancy was used as the denominator for a secondary analysis of preterm delivery rate, miscarriage rate, and caesarean section rate as this helps to give a full picture.
Dealing with missing data
In the situation that data were missing, we contacted trial authors. In situations where attempts for correspondence were unsuccessful, missing data were analysed using intention‐to‐treat basis. Individual values were imputed when missing data included primary outcome live birth rate only: live birth rate were assumed not to have occurred in participants without a reported outcome. We planned that any imputation undertaken would be subjected to sensitivity analysis. For other outcomes, we analysed only the available data.
Assessment of heterogeneity
We considered whether the clinical and methodological characteristics of the included studies were sufficiently similar for meta‐analysis to provide a clinically meaningful summary. Heterogeneity was assessed using the I2 statistic according to the guidelines set out in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). An I2 measurement greater than 50% indicated substantial heterogeneity.
Assessment of reporting biases
In view of the difficulty of detecting and correcting for publication bias and other reporting biases, we aimed to minimise their potential impact by ensuring a comprehensive search for eligible studies and by being alert for duplication of data. If there were 10 or more studies in an analysis, we planned to use a funnel plot to explore the possibility of small‐study effects (a tendency for estimates of the intervention effect to be more beneficial in smaller studies).
Data synthesis
When studies were sufficiently similar, dichotomous data for primary and secondary outcomes were combined using a fixed‐effect model. An increase in the odds of a particular outcome, which may be beneficial (for example live birth) or detrimental (for example preterm delivery), is displayed graphically in the meta‐analysis 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 possible, outcomes were examined in subgroups depending on the type of fibroid (SM, IM and SS).
Sensitivity analysis
For comparisons where primary outcomes were deemed as a high risk of bias, we planned to perform a sensitivity analysis.
Overall quality of the body of evidence: 'Summary of findings' tables
A 'Summary of findings' table was generated using GRADEpro and Cochrane methods (Higgins 2011; GRADEpro GDT 2015). This table evaluated the overall quality of the body of evidence for the main review outcomes (live birth rate, preterm delivery rate, clinical pregnancy rate, ongoing pregnancy rate, caesarean section rate and miscarriage rate) for the main review comparison (myomectomy versus no treatment). Additional 'Summary of findings' tables were prepared for the main review outcomes of other important comparisons (myomectomy performed by laparotomy or mini‐laparotomy versus laparoscopic myomectomy, and monopolar versus bipolar resectoscope use in hysteroscopic myomectomy). The quality of the evidence was assessed using the GRADE criteria: risk of bias, consistency, precision, directness and publication bias. Judgements regarding the evidence quality (high, moderate, low or very low) have been justified, documented, and incorporated into reporting of results for each outcome.
Results
Description of studies
See tables for Characteristics of included studies, Characteristics of excluded studies and Characteristics of ongoing studies
Results of the search
An updated search revealed 1570 articles. Fourteen studies were potentially eligible and were retrieved in full text. Eleven did not fulfil the inclusion criteria and were therefore excluded (Spies 2010; Chatterjee 2012; Kim 2013; Wang 2013; Litta 2014; Seyam 2015; Kramer 2016Wang 2016; Saleh 2018Sato 2018; Wen 2018). Two studies were not included as they were ongoing trials (NCT03143114; NCT03796130). One new study was included (Roy 2017), which was added to the three studies included in the previous version of the review (Seracchioli 2000; Casini 2006; Palomba 2007). Study selection is documented in a Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) flowchart shown in Figure 1.
1.
Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) flowchart.
Included studies
Study design and setting
Four parallel‐design randomised controlled trials (RCTs) were included in the review. Three were single‐centre studies (Seracchioli 2000; Casini 2006; Roy 2017), and one was a multi‐centre study (Palomba 2007) conducted at three university hospitals. Three studies were conducted in Italy and one was conducted in India.
Participants
One study (Casini 2006) compared myomectomy (hysteroscopic myomectomy or myomectomy by laparotomy) to no intervention. It included 92 women in the intervention group and 89 patients in the control group. Two studies compared myomectomy at laparotomy or mini‐laparotomy to laparoscopic myomectomy (Seracchioli 2000; Palomba 2007). These two studies included 86 women in the laparoscopic groups and 91 in the laparotomy/mini‐laparotomy groups. The fourth study (Roy 2017) included women undergoing hysteroscopic myomectomy by either monopolar or bipolar resectoscope and included 34 women for each group.
Three studies included only women suffering from infertility (Seracchioli 2000; Casini 2006; Roy 2017). The fourth study (Palomba 2007), included women with symptomatic fibroids and women with unexplained infertility. Only the women with unexplained infertility were included within the analysis.
Interventions
1/4 studies compared hysteroscopic myomectomy or myomectomy by laparotomy to no treatment (Casini 2006)
2/4 studies compared myomectomy at laparotomy or mini‐laparotomy to laparoscopic myomectomy (Seracchioli 2000; Palomba 2007)
1/4 studies compared monopolar resectoscope use to bipolar resectoscope use in hysteroscopic myomectomy (Roy 2017)
Outcomes
3/4 studies reported live birth (Seracchioli 2000; Palomba 2007; Roy 2017)
2/4 reported preterm delivery (Seracchioli 2000; Palomba 2007)
4/4 studies reported on clinical pregnancy
2/4 reported ongoing pregnancy (Seracchioli 2000; Roy 2017)
4/4 reported miscarriage
2/4 reported caesarean section (Seracchioli 2000; Palomba 2007)
Characteristics of fibroids
Regarding the type of fibroid, only one study subcategorised outcomes by the type of fibroid (Casini 2006). Outcomes were reported separately for intramural; (IM), subserous (SS) and submucous (SM) fibroids as well as combinations of different types. Different methods of surgery were used to perform myomectomy (by either laparotomy or hysteroscopy). However, data were not provided for these techniques separately. The other studies did not specify outcomes by type of fibroid (IM or SS), although authors stated SM fibroids were excluded (Seracchioli 2000; Palomba 2007). The study completed by Roy 2017 evaluated SM fibroids only as the intervention under evaluation in this study permits resection of this type of fibroid only.
Regarding the number and size of fibroid, in the study by Casini 2006, only single fibroids with a maximum diameter of 4 cm were included. Similarly, Roy 2017 included participants with fibroids under 3 cm in diameter, but allowed a maximum of two fibroids. Size and number were more variable in the other two included studies. In the study by Palomba 2007, participants had less than three fibroids, with a diameter between 3 cm and 10 cm. In the study by Seracchioli 2000, a maximum of three fibroids were included with fibroids being 5 cm or more.
Further details of included studies can be found in the table Characteristics of included studies.
Excluded studies
In this version of the review 11 studies were excluded for the following reasons:
10/11 were not RCTs (Spies 2010; Chatterjee 2012; Kim 2013; Wang 2013; Litta 2014; Seyam 2015; Wang 2016; Saleh 2018; Sato 2018; Wen 2018);
1/11 assessed an intervention outside of our review (Kramer 2016).
Characteristics of all excluded studies can be found in the table Characteristics of excluded studies.
Ongoing studies
There are two ongoing clinical trials (NCT03143114; NCT03796130).
Risk of bias in included studies
'Risk of bias' assessment focused on seven domains: generation of allocation sequence, concealment of allocation sequence, blinding of participants and personnel, blinding of outcome assessor, incomplete outcome data, selective outcome reporting and other bias (e.g. publication bias). Details of findings can be found in the relevant 'Risk of bias' summary figure (Figure 2) and the table Characteristics of included studies.
2.
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Allocation
Random sequence generation
All four studies were at low risk of selection bias related to sequence generation as they used computer randomisation or a random numbers table.
Allocation concealment
Two studies were at low risk of selection bias related to allocation concealment as the random allocation sequence was concealed in a closed and dark‐coloured envelope until immediately prior to surgery (Palomba 2007, Roy 2017). The other two studies did not describe the method used and were therefore deemed to have an unclear risk of this bias.
Blinding
Blinding of participants and personnel (performance bias)
As expected, blinding of participants and personnel was not performed in surgical studies. Therefore, the absence of blinding was not considered a source of bias.
Blinding of outcome assessors (detection bias)
It was unclear in all four studies if outcome assessors were blinded to which intervention a participant received.
Incomplete outcome data
All studies analysed all women randomised and we judged them to be at low risk of bias.
Selective reporting
Three of four studies reported on all prespecified outcomes and therefore all three studies were judged to be at low risk of bias (Seracchioli 2000; Casini 2006; Palomba 2007). The fourth study only reported on four of five pre‐specified reproductive outcomes and was therefore deemed high risk of reporting bias (Roy 2017). Furthermore, this study combined outcomes and reported them as a single entity. 'Successful pregnancy outcome' was reported as a combination of live birth rate and ongoing pregnancy rate (> 30 weeks), without explanation. Finally, whilst Casini 2006 reported on all pre‐specified outcomes, it could be considered to be at a high risk of reporting bias as live birth rate was not reported despite the trial lasting seven years.
Other potential sources of bias
We found no other potential sources of bias in any of the included studies.
Effects of interventions
See: Table 1; Table 2; Table 3
Summary of findings for the main comparison. Myomectomy compared to no treatment for fibroids for infertility.
| Myomectomy compared to no treatment for fibroids for infertility | |||||||
| Patient or population: fibroids for infertility Setting: tertiary care Intervention: myomectomy Comparison: no treatment | |||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | Number of participants (studies) | Quality of the evidence (GRADE) | Comments | ||
| Without Myomectomy | With Myomectomy | Difference | |||||
| Live birth rate | No study data available | ||||||
| Preterm delivery rate | No study data available | ||||||
| Clinical pregnancy rate ‐ Intramural | 40.9% | 56.5% (28.3 to 81) | 15.6% more (12.6 fewer to 40 more) | OR 1.88 (0.57 to 6.14) | 45 (1 RCT) | ⊕⊝⊝⊝ VERY LOW a, b | |
| Clinical pregnancy rate ‐ Submucous | 27.3% | 43.3% (18.9 to 71.4) | 16.1% more (8.4 fewer to 44.1 more) | OR 2.04 (0.62 to 6.66) | 52 (1 RCT) | ⊕⊝⊝⊝ VERY LOW a, b | |
| Clinical pregnancy rate ‐ Intramural/Subserous | 21.4% | 35.3% (9.8 to 73.3) | 13.9% more (11.6 fewer to 51.9 more) | OR 2.00 (0.40 to 10.09) | 31 (1 RCT) | ⊕⊝⊝⊝ VERY LOW a, b | |
| Clinical pregnancy rate ‐ Intramural/Submucous | 15.0% | 36.4% (11.3 to 72) | 21.4% more (3.7 fewer to 57 more) | OR 3.24 (0.72 to 14.57) | 42 (1 RCT) | ⊕⊝⊝⊝ VERY LOW a, b | |
| Ongoing pregnancy rate | No study data available | ||||||
| Miscarriage Rate ‐ Intramural | 13.6% | 17.4% (3.9 to 51.7) | 3.8% fewer (9.7 fewer to 38.1 more) | OR 1.33 (0.26 to 6.78) | 45 (1 RCT) | ⊕⊝⊝⊝ VERY LOW a, b | |
| Miscarriage Rate ‐ Submucous | 13.6% | 16.7% (4.1 to 48.5) | 3.1% fewer (9.5 fewer to 34.9 more) | OR 1.27 (0.27 to 5.97) | 52 (1 RCT) | ⊕⊝⊝⊝ VERY LOW a, b | |
| Miscarriage Rate ‐ Intramural/Subserous | 14.3% | 11.8% (1.6 to 52.2) | 2.5% fewer (12.6 fewer to 37.9 more) | OR 0.80 (0.10 to 6.54) | 31 (1 RCT) | ⊕⊝⊝⊝ VERY LOW a, b | |
| Miscarriage Rate ‐ Intramural/Submucous | 10.0% | 18.2% (3.4 to 57.8) | 8.2% fewer (6.6 fewer to 47.8 more) | OR 2.00 (0.32 to 12.33) | 42 (1 RCT) | ⊕⊝⊝⊝ VERY LOW a, b | |
| Caesarean section rate | No study data available | ||||||
| *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). CI: Confidence interval; OR: Odds ratio; RCT: randomised controlled trial. | |||||||
| GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate. | |||||||
a Downgraded two levels for indirectness; population sampled limited (single fibroid of max. 4 cm diameter); outcomes assessed could have included late birth outcome
b Downgraded one level for imprecision; no sample size calculation, there is only one study and small number of events
Summary of findings 2. Laparoscopic myomectomy compared to myomectomy by laparotomy or mini‐laparotomy for fibroids for infertility.
| Laparoscopic myomectomy compared to myomectomy by laparotomy or mini‐laparotomy for fibroids for infertility | |||||||
| Patient or population:fibroids for infertility Setting: tertiary care Intervention: laparoscopic myomectomy Comparison: myomectomy by laparotomy or mini‐laparotomy | |||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | Number of participants (studies) | Quality of the evidence (GRADE) | Comments | ||
| Without Laparoscopic myomectomy | With Laparoscopic myomectomy | Difference | |||||
| Live birth rate | 36.3% | 31.4% (19.3 to 46) | 5.0% fewer (17 fewer to 9.8 more) | OR 0.80 (0.42 to 1.50) | 177 (2 RCTs) | ⊕⊝⊝⊝ VERY LOW a, b, c | |
| Preterm delivery rate | 3.3% | 2.3% (0.4 to 12.8) | 1.0% fewer (2.9 fewer to 9.5 more) | OR 0.70 (0.11 to 4.29) | 177 (2 RCTs) | ⊕⊝⊝⊝ VERY LOW a, b, c | |
| Clinical pregnancy rate | 45.1% | 44.0% (29.9 to 59.3) | 1.0% fewer (15.2 fewer to 14.3 more) | OR 0.96 (0.52 to 1.78) | 177 (2 RCTs) | ⊕⊝⊝⊝ VERY LOW a, b, c | |
| Ongoing pregnancy rate | 3.4% | 5.3% (0.9 to 26.1) | 2.0% more (2.5 fewer to 22.7 more) | OR 1.61 (0.26 to 10.04) | 115 (1 RCT) | ⊕⊝⊝⊝ VERY LOW a, b, c, d | |
| Miscarriage Rate | 6.6% | 8.1% (2.7 to 21.5) | 1.5% more (3.8 fewer to 14.9 more) | OR 1.25 (0.40 to 3.89) | 177 (2 RCTs) | ⊕⊝⊝⊝ VERY LOW a, b, c | |
| Caesarean section rate | 27.5% | 20.9% (11.4 to 34.5) | 6.8% fewer (16.1 fewer to 7 more) | OR 0.69 (0.34 to 1.39) | 177 (2 RCTs) | ⊕⊝⊝⊝ VERY LOW a, b, c, e | |
| *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). CI: Confidence interval; OR: Odds ratio; RCT: randomised controlled trial. | |||||||
| GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate. | |||||||
a Downgraded one level for imprecision; no sample size calculation and small number of events b Downgraded one level for imprecision; odds ratios and confidence intervals show opposing results c Downgraded one level for indirectness; participants with multiple (3 and over), cavity distorting or submucosal fibroids excluded d Downgraded one level for imprecision; only one study e Downgraded one level for inconsistency; significant heterogeneity
Summary of findings 3. Monopolar resectoscope compared to bipolar resectoscope for hysteroscopic myomectomy for infertility.
| Monopolar resectoscope compared to bipolar resectoscope for hysteroscopic myomectomy for infertility | |||||||
| Patient or population: hysteroscopic myomectomy for infertility Setting: tertiary care Intervention: bipolar resectoscope use Comparison: monopolar resectoscope use | |||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | Number of participants (studies) | Quality of the evidence (GRADE) | Comments | ||
| Without Bipolar resectoscope use | With Bipolar resectoscope use | Difference | |||||
| Live birth rate/ ongoing pregnancy ratea | 26.4% | 29.4% (9.7 to 47.4) | 3.5% more (16.7 fewer to 20.9 more) | OR 0.86 (0.30 to 2.50) | 68 (1 RCT) | ⊕⊝⊝⊝ VERY LOW b, c | |
| Preterm delivery rate | No study data available | ||||||
| Clinical pregnancy rate | 33.3% | 38.2% (14.5 to 57) | 3.3% more (20.8 fewer to 21.7 more) | OR 0.88 (0.33 to 2.36) | 68 (1 RCT) | ⊕⊝⊝⊝ VERY LOW b, c | |
| Miscarriage rate | 8.8% | 8.8% (1.8 to 34.1) | 0% fewer (7 fewer to 25.2 more) | OR 1.00 (0.19 to 5.34) | 68 (1 RCT) | ⊕⊝⊝⊝ VERY LOW b, c | |
| Caesarean section rate | No study data available | ||||||
| *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). CI: Confidence interval; OR: Odds ratio; RCT: randomised controlled trial. | |||||||
| GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate. | |||||||
a Authors defined live birth rate/ongoing pregnancy rate > 30 weeks as a 'successful pregnancy outcome' b Downgraded one level for imprecision; sample size calculated but not adhered to, only one study included and small number of events
c Downgraded two levels for indirectness; successful pregnancy outcome which included ongoing pregnancy rate and live birth rate; outcomes intended to be primarily fertility related, however the data presented are primarily surgical outcomes.
1. Comparison of myomectomy versus no intervention.
Results were reported from one study (Casini 2006).
Primary outcomes
1.1 Live birth rate: not reported.
1.2 Preterm delivery rate: not reported.
Secondary outcomes
1.3 Clinical pregnancy rate: we are uncertain whether myomectomy improves clinical pregnancy rate for intramural (IM) fibroids (OR 1.88, 95% CI 0.57 to 6.14, participants = 45; studies = 1; very low‐quality evidence), submucous (SM) fibroids (OR 2.04, 95% CI 0.62 to 6.66; participants = 52; studies = 1; very low‐quality evidence), combined intramural/subserous (IM/SS) fibroids (OR 2.00, 95% CI 0.40 to 10.09; participants = 31; studies = 1; very low‐quality evidence) and combined intramural/submucous (IM/SM) fibroids (OR 3.24, 95% CI 0.72 to 14.57; participants = 42; studies = 1; very low‐quality evidence) (Analysis 1.1: see Figure 3).
1.1. Analysis.
Comparison 1 Myomectomy versus no intervention, Outcome 1 Clinical pregnancy rate.
3.
Forest plot of comparison 1: Myomectomy versus no intervention, Outcome 1.3: Clinical pregnancy rate.
For IM fibroids, chance of pregnancy without myomectomy was assumed to be 41%, compared to between 28% and 81% with myomectomy. For SM fibroids, chance of pregnancy without myomectomy was assumed to be 27%, compared to between 19% and 71% with myomectomy. For IM/SS fibroids, chance of pregnancy without myomectomy was assumed to be 21%, compared to between 10% and 73% with myomectomy. For IM/SM fibroids, chance of pregnancy without myomectomy was assumed to be 15%, compared to between 11% and 72% with myomectomy.
1.4 Ongoing pregnancy rate: not reported.
1.5 Miscarriage rate: we are uncertain whether myomectomy reduces miscarriage rate for IM fibroids (OR 1.33, 95% CI 0.26 to 6.78; 45 participants; one study; very low‐quality evidence), SM fibroids (OR 1.27, 95% CI 0.27 to 5.97; 52 participants; one study; very low‐quality evidence), combined IM/SS fibroids (OR 0.80, 95% CI 0.10 to 6.54; 31 participants; one study; very low‐quality evidence) and combined IM/SM fibroids (OR 2.00, 95% CI 0.32 to 12.33; 42 participants; one study; very low‐quality evidence).
For IM fibroids, chance of miscarriage without myomectomy was 14% compared to between 4% and 52% with myomectomy. For SM fibroids, chance of miscarriage without myomectomy was 14% compared to between 4% and 49% with myomectomy. For IM/SS fibroids, chance of miscarriage without myomectomy was 14% compared to between 2% and 52% with myomectomy. For IM/SM fibroids, chance of miscarriage without myomectomy was 10% compared to between 3% and 58% with myomectomy.
1.6 Caesarean section rate: not reported.
2. Comparison of myomectomy at laparotomy or mini‐laparotomy versus laparoscopic myomectomy
Results were reported from two studies (Seracchioli 2000; Palomba 2007).
Primary outcomes
2.1 Live birth rate: we are uncertain whether laparoscopic myomectomy improves live birth rate compared to myomectomy at laparotomy or mini‐laparotomy (OR 0.80, 95% CI 0.42 to 1.50; participants = 177; studies = 2; I2 = 0%; very low‐quality evidence). This evidence suggests that the birth rate in those receiving myomectomy by laparotomy or mini‐laparotomy is assumed to be 36%, compared to between 19% and 46% for those receiving laparoscopic myomectomy. (Analysis 2.1: see Figure 4).
2.1. Analysis.
Comparison 2 Laparoscopic myomectomy versus myomectomy by laparotomy or mini laparotomy, Outcome 1 Live birth rate.
4.
Forest plot of comparison 2: Laparoscopic myomectomy versus myomectomy at laparotomy or mini‐laparotomy, Outcome 2.1: Live birth rate.
2.2 Preterm delivery rate: we are uncertain whether laparoscopic myomectomy reduces preterm delivery rate compared to myomectomy at laparotomy or mini‐laparotomy (OR 0.70, 95% CI 0.11 to 4.29; participants = 177; studies = 2; I2 = 0%; very low‐quality evidence). This evidence suggests that the preterm delivery rate in those receiving myomectomy by laparotomy or mini‐laparotomy is assumed to be 3%, compared to between 0% and 13% for those receiving laparoscopic myomectomy. (Analysis 2.2: see Figure 5).
2.2. Analysis.
Comparison 2 Laparoscopic myomectomy versus myomectomy by laparotomy or mini laparotomy, Outcome 2 Preterm delivery rate.
5.
Forest plot of comparison 2: Laparoscopic myomectomy versus myomectomy at laparotomy or mini‐laparotomy, Outcome 2.2: Preterm delivery rate.
Secondary outcomes
2.3 Clinical pregnancy rate: we are uncertain whether laparoscopic myomectomy improves clinical pregnancy rate compared to myomectomy at laparotomy or mini‐laparotomy (OR 0.96, 95% CI 0.52 to 1.78; participants = 177; studies = 2; I2 = 0%; very low‐quality evidence) (Analysis 2.3). This evidence suggests that the clinical pregnancy rate in those receiving myomectomy by laparotomy or mini‐laparotomy is 45% compared to between 30% and 59% receiving laparoscopic myomectomy.
2.3. Analysis.
Comparison 2 Laparoscopic myomectomy versus myomectomy by laparotomy or mini laparotomy, Outcome 3 Clinical pregnancy rate.
2.4 Ongoing pregnancy rate: we are uncertain whether laparoscopic myomectomy improves ongoing pregnancy rate compared to myomectomy at laparotomy or mini‐laparotomy (OR 1.16, 95% CI 0.26 to 10.04, participants = 115; studies = 1; very low‐quality evidence) (Analysis 2.4). This evidence suggests that the chances of an ongoing pregnancy in those receiving myomectomy by laparotomy or mini‐laparotomy is assumed to be 3%, the chance with laparoscopic myomectomy would be between 1% and 26%.
2.4. Analysis.
Comparison 2 Laparoscopic myomectomy versus myomectomy by laparotomy or mini laparotomy, Outcome 4 Ongoing pregnancy rate.
2.5 Miscarriage rate: we are uncertain whether laparoscopic myomectomy reduces miscarriage rate compared to myomectomy at laparotomy or mini‐laparotomy (OR 1.25, 95% CI 0.40 to 3.89; participants = 177; studies = 2; I2 = 0%; very low‐quality evidence) (Analysis 2.5). This evidence suggests that the chances of a miscarriage in those receiving myomectomy by laparotomy or mini‐laparotomy is assumed to be 7%, the chance with laparoscopic myomectomy would be between 3% and 22%.
2.5. Analysis.
Comparison 2 Laparoscopic myomectomy versus myomectomy by laparotomy or mini laparotomy, Outcome 5 Miscarriage rate.
2.6 Caesarean section rate: we are uncertain whether laparoscopic myomectomy improves caesarean section rate compared to myomectomy at laparotomy or mini‐laparotomy (OR 0.69, 95% CI 0.34 to 1.39; participants = 177; studies = 2; I2 = 21%; very low‐quality evidence) (Analysis 2.6). This evidence suggests that the chances of having a caesarean section in those receiving myomectomy by laparotomy or mini‐laparotomy is assumed to be 28%, compared to between 11% and 35% in those receiving laparoscopic myomectomy.
2.6. Analysis.
Comparison 2 Laparoscopic myomectomy versus myomectomy by laparotomy or mini laparotomy, Outcome 6 Caesarean section rate.
3. Comparison of monopolar versus bipolar resectoscope use in hysteroscopic myomectomy
Results were reported from one study (Roy 2017).
Primary outcomes
3.1 Live birth/ongoing pregnancy rate (defined by authors as a 'successful pregnancy outcome' > 30 weeks): we are uncertain whether bipolar resectoscope use improves live birth/ongoing pregnancy rate compared to monopolar resectoscope use in hysteroscopic myomectomy (OR 0.86, 95% CI 0.30 to 2.50, participants = 68; studies = 1; very low‐quality evidence). Therefore meaning that in those receiving monopolar resectoscope use in hysteroscopic myomectomy, the birth rate was assumed to be 26.4%, compared to between 10% and 47% in those who had a myomectomy with a bipolar resectoscope. (Analysis 3.1: see Figure 6).
3.1. Analysis.
Comparison 3 Monopolar versus bipolar resectoscope use in hysteroscopic myomectomy, Outcome 1 Live birth rate/ongoing pregnancy rate.
6.
Forest plot of comparison 3: Monopolar versus bipolar resectoscope use in hysteroscopic myomectomy, Outcome 3.1 Live birth rate/Ongoing pregnancy rate.
3.2 Preterm delivery rate: not reported.
Secondary outcomes
3.3 Clinical pregnancy rate: we are uncertain whether bipolar resectoscope use improves clinical pregnancy rate compared to monopolar resectoscope use in hysteroscopic myomectomy (OR 0.88, 95% CI 0.33 to 2.36, participants = 68; studies = 1; very low‐quality evidence) (Analysis 3.2). Therefore meaning that in those receiving a myomectomy using a monopolar resectoscope, clinical pregnancy rate was assumed to be 33.3%, compared to between 15% and 57% in those who had a myomectomy with a bipolar resectoscope.
3.2. Analysis.
Comparison 3 Monopolar versus bipolar resectoscope use in hysteroscopic myomectomy, Outcome 2 Clinical pregnancy rate.
3.4 Ongoing pregnancy rate: reported above with live birth rate.
3.5 Miscarriage rate: we are uncertain whether bipolar resectoscope use reduces miscarriage rate compared to monopolar resectoscope use in hysteroscopic myomectomy (OR 1.00, 95% CI 0.19 to 5.34; participants = 68; studies = 1; very low‐quality evidence) (Analysis 3.3). Therefore meaning that in those receiving a myomectomy using a monopolar resectoscope, miscarriage rate was assumed to be 9%, compared to between 2% and 34% in those who had a myomectomy with a bipolar resectoscope.
3.3. Analysis.
Comparison 3 Monopolar versus bipolar resectoscope use in hysteroscopic myomectomy, Outcome 3 Miscarriage rate.
3.6 Caesarean section rate: not reported.
Effects of subgroup analysis
Subgroup analysis permitted examination of effect of intervention on fibroids in different locations. Only one study reported on location of fibroids individually, which meant there were too few studies to perform the planned subgroup analysis.
Effects of sensitivity analysis
As no single comparison included a study with a primary outcome deemed as a high risk of bias, a sensitivity analysis was not performed. Furthermore, there were too few studies to conduct sensitivity analysis.
Discussion
Summary of main results
This review included four randomised controlled studies (RCTs) (442 participants) that examined the effect of myomectomy on fertility outcomes. When examining this issue, two questions need to be answered. Firstly, whether myomectomy leads to an improvement in fertility outcomes; and secondly, if there is a beneficial effect what would be the ideal surgical approach?
The first question was addressed by only one randomised controlled trial (Casini 2006). This study appropriately examined reproductive outcomes separately for the different types of fibroids. We are uncertain of the effect myomectomy had on both clinical pregnancy and miscarriage rate compared to no treatment. Unfortunately this study did not report on either primary outcome (live birth rate or preterm delivery rate), despite the study lasting seven years. Furthermore, the study collectively reported on myomectomies performed either by laparotomy or hysteroscopy, meaning separate analysis of these two very different surgical approaches could not be performed.
The second question was addressed by three studies (Seracchioli 2000, Palomba 2007 and Roy 2017). Two studies compared myomectomy at laparotomy or mini‐laparotomy to laparoscopic myomectomy (Palomba 2007; Seracchioli 2000). It is uncertain which surgical method is superior when comparing these approaches on fertility outcomes (live birth, preterm delivery, clinical pregnancy, ongoing pregnancy, miscarriage and caesarean section rate). The third study (Roy 2017) compared monopolar versus bipolar resectoscope use in hysteroscopic myomectomy. It is uncertain which of the two approaches is superior regarding any of the reported fertility outcomes (live birth rate, clinical pregnancy rate and miscarriage rate).
Overall completeness and applicability of evidence
1. In determining the effect of myomectomy on fertility outcomes, fibroids are not a single entity but vary widely regarding site and size with different fertility effects being reported for intramural (IM), subserous (SS) and submucous (SM) fibroids. There is currently a consensus regarding the fertility effects for SS and SM fibroids, based on the findings of several case‐controlled studies and meta‐analyses. These studies suggest SM fibroids have been found to be associated with a negative impact on fertility while SS fibroids appeared to have little to no effect (Pritts 2009). Opinion regarding IM fibroids is more controversial. Some studies have suggested a negative effect on fertility (Pritts 2009; Sunkara 2010), while a more recent study has suggested that in fact the quality of evidence is too low to draw any conclusions (Metwally 2011). In the midst of such controversy, clinicians are left with a difficult task when deciding whether or not to surgically intervene, particularly when surgical intervention may itself pose a risk to fertility due to the risk of intrauterine and pelvic adhesions.
Unfortunately the current evidence does not settle this dilemma as only one study addressed reproductive outcomes separately for different types of fibroids (Casini 2006). The sample size was relatively small and therefore inadequate to draw a firm conclusion. Furthermore, the study was limited only to single fibroids of a maximum size of 4 cm. Finally, the study did not report on the live birth rate.
2. For type of surgical approach, evidence regarding the use of laparoscopy versus laparotomy was more comprehensive. While the use of the laparoscopic approach may offer advantages regarding postoperative recovery and morbidity, the current study was unable to identify any clear benefit for the laparoscopic approach regarding fertility outcomes. On the positive side, despite the small number of studies, both studies provided evidence regarding our primary outcome, live birth rate, as well as several secondary outcomes. Furthermore, information is provided regarding late pregnancy outcomes, that is preterm delivery and caesarean section rates. However, the difficulty with comparing the two abdominal approaches remains the fact that there is a large variation in surgical practice, for example level of skill, surgical technique and use of anti‐adhesion agents, all of which may influence fertility outcomes. Therefore, until a larger number of studies is available, it would be difficult to draw a firm conclusion. Finally, SM fibroids are thought to have the strongest association with impaired fertility, with hysteroscopic myomectomy considered the most appropriate surgical approach. Despite the potential fertility implications, there is limited high‐quality evidence available evaluating the intervention on reproductive outcomes. Only one RCT, attempts to make progress analysing this approach (Roy 2017). This study compared electrosurgical systems (monopolar to bipolar). Previously, both techniques have been shown to have successful pregnancy outcomes (Makris 2007; Litta 2014a). Results found that there was minimal difference between the two interventions on reproductive outcomes. Outside of our assessed outcomes, a greater difference was seen. Bipolar resectoscope use had better surgical outcomes, suggesting it would be a safer alternative.
Quality of the evidence
For the effect of myomectomy on fertility outcomes, the study by Casini 2006 had the advantage of clearly defining the type of fibroid, by only including single fibroids of 4 cm maximum diameter. Information regarding larger or multiple fibroids is however clearly lacking. Allocation concealment was not clear raising the possibility of selection bias. Furthermore, abdominal myomectomies and hysteroscopic myomectomies are two very different techniques dealing with different types of fibroids and with very different potential side effects that may have a negative impact on fertility (that is intrauterine versus peritubal adhesions). Therefore the inclusion of these two surgical approaches into one study group has the potential to introduce bias and further compromise the quality of the evidence.
For the surgical approach for myomectomy, three studies provided evidence. Only two studied myomectomy at laparotomy or mini‐laparotomy compared to laparoscopic myomectomy (Seracchioli 2000; Palomba 2007), and therefore the evidence should be viewed with caution. The study by Seracchioli 2000 was not clear regarding allocation concealment. However a positive aspect of the analysis is that all outcomes were associated with no evidence of significant heterogeneity. The fourth study compared monopolar resectoscope use to bipolar resectoscope use in hysteroscopic myomectomy. As only one study provided evidence for this comparison, with only 60 participants, evidence must be viewed with caution. This study did perform a power calculation (Roy 2017). However, only 60 participants in total were recruited, despite the completed power calculation indicating needing a threshold of 100 participants per group for significant findings. Furthermore, this study had a high risk of reporting bias, as intended outcomes did not match reported outcomes.
Overall, the quality of evidence in this review was very low quality. Three studies included in the review did not perform a power calculation or explain the rationale behind their recruited sample size (Seracchioli 2000; Casini 2006; Palomba 2007). Furthermore, Palomba 2007 describes halting recruitment following an interim analysis due to quote "too little or clinically irrelevant difference in outcomes to continue the study to obtain an adequate power". As described by Kadam 2010, a sample size should always be performed prior to starting a trial and should not be altered during the study, meaning all three studies are likely to be underpowered and can be criticised.
Potential biases in the review process
Review authors MM and GR independently screened and identified relevant studies making it unlikely that any studies have been missed. Furthermore, a final search was performed at the completion of the review to ensure that no new studies had been published during preparation of the manuscript. However, despite all our efforts, there is still a possibility that studies in press may have been missed.
All review authors were in agreement regarding the inclusion or exclusion of any newly identified study, and therefore it is unlikely that a misjudgement has been made leading to the non‐inclusion of any relevant study.
Agreements and disagreements with other studies or reviews
This review remains the only systematic review and meta‐analysis to assess the role of myomectomy on fertility outcomes. SInce the review was last updated in 2012 (Metwally 2012), one new study has been included (Roy 2017) and primary outcomes have been reassessed. The previous version included two comparisons evaluating myomectomy compared to no treatment and different surgical approaches to myomectomy. The addition of a new study has permitted an expansion of the review to include a third comparison evaluating use of different electrosurgical systems in hysteroscopic myomectomy. Additionally, preterm delivery rate has been promoted to a primary outcome.The main findings however remain unchanged, where the insufficient number of studies prevents us from drawing a firm conclusion.
Authors' conclusions
Implications for practice.
There remains limited evidence to determine the role of myomectomy for infertility in women with fibroids. If the decision is made to have a myomectomy, the current evidence does not indicate a superior method (laparoscopy, laparotomy or different electrosurgical systems) to improve rates of live birth, preterm delivery, clinical pregnancy, ongoing pregnancy, miscarriage, or caesarean section. Furthermore, the existing evidence needs to be viewed with caution due to the small number of events, minimal number of studies and very low‐quality evidence.
Implications for research.
There is an urgent need for high‐quality randomised controlled studies to determine the role of myomectomy for fertility management, given that fibroids are not a single entity but a wide spectrum of tumours. Studies should therefore take into consideration the following points.
Priority should be given to studies comparing myomectomy to no intervention rather than comparing different types of surgical interventions. If a beneficial effect for surgery is demonstrated then the next step would be to focus on the type of surgical approach.
Studies should classify outcomes by the size and type of fibroid (intramural (IM), subserous (SS) and submucous (SM)) with clear definitions in the inclusion and exclusion criteria.
Inclusion of patients in future studies with only unexplained infertility would minimise the effect of other confounding factors such as differences in the cause of infertility.
What's new
| Date | Event | Description |
|---|---|---|
| 6 June 2019 | New citation required but conclusions have not changed | The addition of one new included study has not changed the conclusions of this review. |
| 6 June 2019 | New search has been performed | New study included: Roy 2017 Eleven studies excluded: Spies 2010; Chatterjee 2012; Kim 2013; Wang 2013; Litta 2014; Seyam 2015; Kramer 2016; Wang 2016; Saleh 2018; Sato 2018; Wen 2018; Two ongoing clinical trials NCT03143114; NCT03796130. Primary and secondary outcome measures have been updated and modified. Live birth rate remained the primary effectiveness measure. Preterm delivery was promoted to a primary outcome as the primary safety measure as it is the leading cause of neonatal mortality. Methods sections updated to reflect CGF policy e.g. ensuring the denominator for the primary analyses is per woman randomised. |
History
Protocol first published: Issue 4, 2002 Review first published: Issue 3, 2006
| Date | Event | Description |
|---|---|---|
| 12 September 2012 | New citation required but conclusions have not changed | There remains insufficient evidence for performing myomectomy to improve fertility. |
| 29 August 2012 | New search has been performed | Summary of findings tables generated from GRADE software and incorporated in review. 2 new studies included: Casini 2006; Palomba 2007; 3 studies excluded: Bulletti 2004; Chang 2011; Shokeir 2010. Primary and secondary outcome measures have been updated and modified. The primary outcome measure is live birth rate, while secondary outcomes include: ongoing pregnancy rate, miscarriage rate, clinical pregnancy rate, caesarean section and preterm delivery rates. |
| 17 November 2010 | New search has been performed | Updated searches performed |
| 6 November 2008 | Amended | Converted to new review format. |
| 15 May 2006 | New citation required and conclusions have changed | Substantive amendment |
Acknowledgements
This review is an updated version of the initial Cochrane review by Anthony N Griffiths, Arianna D'Angelo and Nazar N Amso (Griffiths 2006). We would like to acknowledge their valuable contribution.
Appendices
Appendix 1. Cochrane Gynaecology and Fertility Group's specialised register search strategy
Searched 26 February 2019
Procite platform
Keywords CONTAINS "fibroid" or "Leiomyoma*" or "myoma" or "myomas" or "uterine leiomyomas" or "uterine myoma" or "uterine myomas" or "uterine fibroids" or "fibroids" or Title CONTAINS "fibroid" or "Leiomyoma*" or "myoma" or "myomas" or "uterine leiomyomas" or "uterine myoma" or "uterine myomas" or "uterine fibroids" or "fibroids"
AND
Keywords CONTAINS "surgery" or "surgery‐gynaecological" or "surgery vs medicine" or "Surgical" or "*Surgical‐Procedures,‐Laparoscopic" or "surgical treatment" or "myomectomy" or "laparoscopic myomectomy" or "laparoscopic procedure" or "laparoscopic surgical treatment" or "laparotomy" or "hysteroscopic surgery" or "hysteroscopy" or "microlaparoscopy" or "microsurgery" or Title CONTAINS "surgery" or "surgery‐gynaecological" or "surgery vs medicine" or "Surgical" or "*Surgical‐Procedures,‐Laparoscopic" or "surgical treatment" or "myomectomy" or "laparoscopic myomectomy" or "laparoscopic procedure" or "laparoscopic surgical treatment" or "laparotomy" or "hysteroscopic surgery" or "hysteroscopy" or "microlaparoscopy" or "microsurgery"
(408 records)
Appendix 2. CENTRAL via Cochrane Central Register of Studies Online (CRSO) search strategy
Searched 26 February 2019
Web platform
#1 MESH DESCRIPTOR Leiomyoma EXPLODE ALL TREES 584
#2 MESH DESCRIPTOR Myoma EXPLODE ALL TREES 24
#3 (Leiomyoma* or fibroid*):TI,AB,KY 1091
#4 (uter* adj5 fibroma*):TI,AB,KY 13
#5 (myom* or hysteromyom* or fibromyom*):TI,AB,KY 1560
#6 #1 OR #2 OR #3 OR #4 OR #5 2125
#7 MESH DESCRIPTOR Gynecologic Surgical Procedures EXPLODE ALL TREES 4028
#8 MESH DESCRIPTOR Laparoscopy EXPLODE ALL TREES 5124
#9 MESH DESCRIPTOR Hysteroscopy EXPLODE ALL TREES 363
#10 MESH DESCRIPTOR Uterine Myomectomy EXPLODE ALL TREES 46
#11 MESH DESCRIPTOR Microsurgery EXPLODE ALL TREES 614
#12 MESH DESCRIPTOR Laparotomy EXPLODE ALL TREES 701
#13 (microsurg* or surg*):TI,AB,KY 173032
#14 (Laparoscop* or minilaparoscop*):TI,AB,KY 13570
#15 Hysteroscop* :TI,AB,KY 1037
#16 myomectom*:TI,AB,KY 535
#17 (Laparotom* or minilaparotom*):TI,AB,KY 2489
#18 #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 177578
#19 #6 AND #18 1158
#20 2012 TO 2019:YR 514326
#21 01/01/2012 TO 26/02/2019:CD 643072
#22 #20 OR #21 643083
#23 #19 AND #22 673
Appendix 3. MEDLINE search strategy
Searched from 1946 to 26 February 2019
OVID platform
1. exp Leiomyoma/ (20114)
2. (Leiomyoma$ or fibroid$).tw. (18116)
3. (uter$ adj5 fibroma$).tw. (405)
4. exp Myoma/ (2716)
5. (myom$ or hysteromyom$ or fibromyom$).tw. (23071)
6. or/1‐5 (44362)
7. exp Gynecologic Surgical Procedures/ (78898)
8. microsurg$.tw. (23975)
9. exp hysteroscopy/ or exp laparoscopy/ (94599)
10. exp Uterine Myomectomy/ (742)
11. exp Microsurgery/ (32013)
12. exp Laparotomy/ (18164)
13. (Laparoscop$ or minilaparoscop$).tw. (115957)
14. Hysteroscop$.tw. (6391)
15. surg$.tw. (1760957)
16. myomectom$.tw. (3318)
17. Laparotom$.tw. (46459)
18. minilaparotom$.tw. (1030)
19. or/7‐18 (1906437)
20. 6 and 19 (14784)
21. randomized controlled trial.pt. (476544)
22. controlled clinical trial.pt. (92921)
23. randomized.ab. (435206)
24. placebo.tw. (200882)
25. clinical trials as topic.sh. (186073)
26. randomly.ab. (305887)
27. trial.ti. (194540)
28. (crossover or cross‐over or cross over).tw. (79266)
29. or/21‐28 (1227748)
30. exp animals/ not humans.sh. (4549808)
31. 29 not 30 (1127992)
32. 20 and 31 (873)
Appendix 4. Embase search strategy
Searched from 1980 to 26 February 2019
OVID platform
1. exp leiomyoma/ or exp uterus myoma/ (29328)
2. (Leiomyoma$ or fibroid$).tw. (24016)
3. (uter$ adj5 fibroma$).tw. (345)
4. (myom$ or hysteromyom$ or fibromyom$).tw. (28853)
5. or/1‐4 (54814)
6. exp Gynecologic Surgical Procedures/ or exp uterus surgery/ (134198)
7. microsurg$.tw. (27861)
8. exp microsurgery/ or exp myotomy/ (37988)
9. exp Laparotomy/ (70673)
10. (Laparoscop$ or minilaparoscop$).tw. (184220)
11. exp Laparoscopy/ (146549)
12. Hysteroscop$.tw. (10932)
13. exp hysteroscopy/ (11137)
14. surg$.tw. (2244163)
15. exp Uterine Myomectomy/ (6335)
16. myomectom$.tw. (5791)
17. Laparotom$.tw. (59834)
18. minilaparotom$.tw. (1307)
19. or/6‐18 (2451389)
20. Clinical Trial/ (944597)
21. Randomized Controlled Trial/ (533054)
22. exp randomization/ (81333)
23. Single Blind Procedure/ (33971)
24. Double Blind Procedure/ (155315)
25. Crossover Procedure/ (58216)
26. Placebo/ (316874)
27. Randomi?ed controlled trial$.tw. (197224)
28. Rct.tw. (31346)
29. random allocation.tw. (1859)
30. randomly allocated.tw. (31715)
31. allocated randomly.tw. (2398)
32. (allocated adj2 random).tw. (799)
33. Single blind$.tw. (22115)
34. Double blind$.tw. (188192)
35. ((treble or triple) adj blind$).tw. (902)
36. placebo$.tw. (279419)
37. prospective study/ (501549)
38. or/20‐37 (1982692)
39. case study/ (59090)
40. case report.tw. (363254)
41. abstract report/ or letter/ (1049465)
42. or/39‐41 (1462477)
43. 38 not 42 (1932607)
44. 5 and 19 and 43 (2735)
Appendix 5. PsycINFO search strategy
Searched from 1806 to 26 February 2019
OVID platform
1. (Leiomyoma$ or fibroid$).tw. (77)
2. (uter$ adj5 fibroma$).tw. (4)
3. (myoma$ or hysteromyoma$ or fibromyom$).tw. (29)
4. or/1‐3 (109)
5. exp surgery/ (54923)
6. microsurg$.tw. (232)
7. Laparoscop$.tw. (468)
8. Hysteroscop$.tw. (17)
9. surg$.tw. (46504)
10. myomectom$.tw. (11)
11. Laparotom$.tw. (158)
12. or/5‐11 (84377)
13. 4 and 12 (43)
14. random.tw. (54555)
15. control.tw. (419970)
16. double‐blind.tw. (21948)
17. clinical trials/ (11241)
18. placebo/ (5205)
19. exp Treatment/ (725477)
20. or/14‐19 (1134175)
21. 13 and 20 (31)
Appendix 6. CINAHL search strategy
Searched from 1961 to 26 February 2019
EBSCO platform
| # | Query | Results |
| S32 | S19 AND S31 | 322 |
| S31 | S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 | 1,304,565 |
| S30 | TX allocat* random* | 9,874 |
| S29 | (MH "Quantitative Studies") | 21,853 |
| S28 | (MH "Placebos") | 11,144 |
| S27 | TX placebo* | 55,420 |
| S26 | TX random* allocat* | 9,874 |
| S25 | (MH "Random Assignment") | 53,511 |
| S24 | TX randomi* control* trial* | 163,780 |
| S23 | TX ( (singl* n1 blind*) or (singl* n1 mask*) ) or TX ( (doubl* n1 blind*) or (doubl* n1 mask*) ) or TX ( (tripl* n1 blind*) or (tripl* n1 mask*) ) or TX ( (trebl* n1 blind*) or (trebl* n1 mask*) ) | 1,003,357 |
| S22 | TX clinic* n1 trial* | 238,860 |
| S21 | PT Clinical trial | 86,752 |
| S20 | (MH "Clinical Trials+") | 254,336 |
| S19 | S6 AND S18 | 2,222 |
| S18 | S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 | 47,294 |
| S17 | TX minilaparotom* | 116 |
| S16 | TX Laparotom* | 6,681 |
| S15 | TX myomectom* | 1,051 |
| S14 | (MM "Surgery, Laparoscopic+") | 4,407 |
| S13 | TX Hysteroscop* | 2,058 |
| S12 | (MM "Hysteroscopy") | 872 |
| S11 | TX Laparoscop* or TX minilaparoscop* | 30,260 |
| S10 | (MM "Laparotomy") | 1,092 |
| S9 | (MM "Microsurgery+") | 1,614 |
| S8 | TX microsurg* | 3,913 |
| S7 | (MM "Surgery, Gynecologic+") | 8,805 |
| S6 | S1 OR S2 OR S3 OR S4 OR S5 | 6,654 |
| S5 | TX myom* or TX hysteromyom* or TX fibromyom* | 2,989 |
| S4 | (MM "Myoma+") | 213 |
| S3 | TX uter* N5 fibroma* | 21 |
| S2 | TX Leiomyoma* or TX fibroid* | 4,606 |
| S1 | (MM "Leiomyoma") | 2,684 |
Appendix 7. Data extraction form
| Data extraction form | Findings |
| Title | |
| Authors | |
| Journal | |
| Year | |
| DOI | |
| Location | |
| Study design | |
| Participants (plus inclusion and exclusion criteria) | |
| Intervention | |
| Comparison | |
| Outcomes | |
| Other | |
| Risk of bias |
Data and analyses
Comparison 1. Myomectomy versus no intervention.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Clinical pregnancy rate | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Intramural | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 1.2 Submucous | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 1.3 Intramural/Subserous | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 1.4 Intramural/Submucous | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 2 Miscarriage rate | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 2.1 Intramural | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 2.2 Submucous | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 2.3 Intramural/Subserous | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 2.4 Intramural/Submucous | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
1.2. Analysis.
Comparison 1 Myomectomy versus no intervention, Outcome 2 Miscarriage rate.
Comparison 2. Laparoscopic myomectomy versus myomectomy by laparotomy or mini laparotomy.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Live birth rate | 2 | 177 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.80 [0.42, 1.50] |
| 2 Preterm delivery rate | 2 | 177 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.70 [0.11, 4.29] |
| 3 Clinical pregnancy rate | 2 | 177 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.96 [0.52, 1.78] |
| 4 Ongoing pregnancy rate | 1 | 115 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.61 [0.26, 10.04] |
| 5 Miscarriage rate | 2 | 177 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.25 [0.40, 3.89] |
| 6 Caesarean section rate | 2 | 177 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.34, 1.39] |
Comparison 3. Monopolar versus bipolar resectoscope use in hysteroscopic myomectomy.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Live birth rate/ongoing pregnancy rate | 1 | 68 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.86 [0.30, 2.50] |
| 2 Clinical pregnancy rate | 1 | 68 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.88 [0.33, 2.36] |
| 3 Miscarriage rate | 1 | 68 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.0 [0.19, 5.34] |
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Casini 2006.
| Methods | Randomised controlled trial | |
| Participants | 181 participants Treatment n = 92, No treatment = 89 Treatment (SM n = 30, IM n = 23, IM/SS n = 17, SM/IM n = 22) No treatment (SM n = 22, IM n = 22, SS n = 11, IM/SS n = 14, SM/IM n = 20) Participants woman with infertility and fibroids, with no other cause for infertility. Inclusion criteria: 1‐ age: < 35 years; 2‐ infertility for 1 year or more; 3‐ presence of one fibroid with maximum diameter of 40 mm. Exclusion criteria: 1‐ two or more fibroids with diameter more than 40 mm; 2‐ body weight more than 20% above normal weight; 3‐ use of medication containing oestrogens, progestins or androgens within 8 weeks prior to starting the study. |
|
| Interventions | Myomectomy at hysteroscopy or laparotomy or no intervention | |
| Outcomes | 1‐ Clinical pregnancy rate, defined as visualisation of an embryo with cardiac activity at 6–7 weeks of pregnancy. 2‐ Miscarriage rate, defined as clinical loss of an intrauterine pregnancy between 7th and 12th weeks of gestation. |
|
| Notes | No power calculation Follow‐up period: 12 months Funding: none stated Conflict of interest: none stated Study dates: 1998‐2005 Trial registration number: unknown |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation table |
| Allocation concealment (selection bias) | Unclear risk | Not mentioned |
| Blinding of participants and personnel (Performance bias) All outcomes | Low risk | Due to the nature of the intervention, personnel could not be blinded. Furthermore, participants could not be blinded as they either received surgery or did not. Therefore, performance bias was not considered a source of bias in this study. |
| Blinding of outcome assessors (Detection bias) All outcomes | Unclear risk | It remains unclear whether outcome assessors were blinded when analysis results (detection bias) |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Outcomes reported for all patients who started the study |
| Selective reporting (reporting bias) | Low risk | All specified outcomes reported in the results section |
| Other bias | Low risk | No evidence of other bias |
Palomba 2007.
| Methods | Randomised controlled trial | |
| Participants | 136 participants Participants had either symptomatic uterine leiomyomas (n = 74) or infertility (n = 62). Only unexplained fertility patients were analysed Laparoscopy n = 30 Laparotomy n = 32 Exclusion criteria: patient characteristics:1‐ major medical conditions and endocrine diseases, 2‐ basal FSH >10 IU/L, 3‐ psychiatric disorders, 4‐ current or past history of acute or chronic physical illness, 5‐ premenstrual syndrome, 6‐ current or past (within 6 months) use of hormonal medications, 7‐ medications influencing cognition, vigilance, or mood, 8‐ inability to complete the daily diary, 9‐ history of alcohol abuse, tubal or male factor infertility, 10‐ no desire to conceive. Myoma characteristics: 1‐ three or more uterine fibroids, 2‐fibroids with a main diameter less than 3 cm, 3‐ fibroids with a mean diameter of more than 10 cm, 4‐ hypoechoic or calcified fibroids, 5‐ presence of submucosal fibroids, 6‐ uterine cavity distortion diagnosed by hysteroscopy, 7‐ other uterine or adnexal abnormalities at ultrasound, 8‐ endometrial hyperplasia or atypia, 9‐ abnormal cervical smear. |
|
| Interventions | Laparoscopic myomectomy or myomectomy by minilaparotomy | |
| Outcomes | 1‐ Cumulative pregnancy rate: calculated as the ratio between number of pregnant women and total number of patients studied. 2‐ Cumulative live birth rate: calculated as women with a baby alive over the total number of pregnant women. 3‐ Miscarriage rate: defined as the ratio between number of miscarriages during the first 12 weeks of gestation and total pregnancies. 4‐ Pregnancy rate and live birth rates per cycle, defined as the ratio between number of pregnancies and live births, respectively, and the total number of cycles studied. |
|
| Notes | No power calculation. Only the subgroup of patients with unexplained infertility were included in the meta‐analysis. Follow‐up period: 12 months. Those obtaining pregnancy within 12 months were followed up for another 9 months Funding: none stated Conflict of interest: none stated Study dates: 2002‐2003 Trial registration number: unknown The study was approved by the Institutional Review Board (IRB) of the University “Magna Graecia” of Catanzaro, Italy |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation performed using online software (www.randomization.it) |
| Allocation concealment (selection bias) | Low risk | The random allocation sequence was concealed in a closed and dark‐coloured envelope until immediately prior to surgery |
| Blinding of participants and personnel (Performance bias) All outcomes | Low risk | Due to the nature of the intervention, personnel could not be blinded. Furthermore, participants could not be blinded to which intervention they received as the surgical incisions varied between interventions. Therefore, performance bias was not considered a source of bias in this study, |
| Blinding of outcome assessors (Detection bias) All outcomes | Unclear risk | It remains unclear whether outcome assessors were blinded when analysing results (detection bias) |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Outcomes reported for all patients who started the study |
| Selective reporting (reporting bias) | Low risk | All specified outcomes reported in the results section |
| Other bias | Low risk | No evidence of other bias |
Roy 2017.
| Methods | Randomised controlled trial | |
| Participants | 68 participants Monopolar n =34 Bipolar n =34 Participants infertile women with submucous fibroids The inclusion criteria were the following: (1) submucous myoma of Type 0 FIGO PALM COEIN classification diagnosed during outpatient hysteroscopy, (2) history of infertility, (3) age less than 35 years, (5) written informed consent, and (6) normal semen parameters of the husband The exclusion criteria were the following: (1) patients with any other known cause of infertility were excluded from the study, (2) the presence of fibroid other than Type 0 FIGO PALM COEIN classification, (3) fibroid size more than 3 cm, or (4) more than 2 myomas |
|
| Interventions | Hysteroscopic myomectomy using monopolar or bipolar resectoscope | |
| Outcomes | Primary outcomes: pregnancy‐related indicators (improvement in menstrual symptoms, clinical pregnancy rate, abortion rate, live birth rate/ongoing pregnancy rate > 30 weeks) Secondary outcomes: operative parameters, harmful outcomes related to the procedure, and comparison of improvement levels in the menstrual pattern after surgery between the two groups |
|
| Notes | Authors were contacted regarding gathering data for our primary outcome live birth rate. Live birth rate is dual reported with ongoing pregnancy rate > 30 weeks in the article. Authors did not respond to our attempts to contact them. Power calculation was performed but not adhered to. Follow‐up period: a minimum of 12 months (no average or maximum follow‐up period was stated) Funding: authors state no funding given Conflict of interest: authors state no conflict of interest Study dates: 2012‐2016 Trial registration number: unknown |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Participants were randomised into two groups using Epi‐Info version 7.0 software |
| Allocation concealment (selection bias) | Low risk | Allocation sequence was concealed and stapled envelopes were handed to the statistician |
| Blinding of participants and personnel (Performance bias) All outcomes | Low risk | Participants were blinded to which intervention they received. Due to the nature of the intervention, personnel could not be blinded. Therefore, performance bias was not considered a source of bias in this study, |
| Blinding of outcome assessors (Detection bias) All outcomes | Unclear risk | It remains unclear whether outcome assessors were blinded when analysing results (detection bias) |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Outcomes reported for all participants that started the study |
| Selective reporting (reporting bias) | High risk | Four of five prespecified reproductive outcomes were reported on |
| Other bias | Low risk | No evidence of other bias |
Seracchioli 2000.
| Methods | Randomised controlled trial | |
| Participants | 131 participants Laparoscopy n = 56 Laparotomy n = 59 Participants infertile women with at least one myoma greater than 5 cm. Inclusion criteria: infertile women with infertility and fibroids. Exclusion criteria: 1‐ pedunculated fibroids 2‐ uterine size above the umbilicus 3‐more than three fibroids > 5 cm in diameter 4‐ associated other causes of infertility such as tubal or male factor 5‐ uterine cavity abnormalities. |
|
| Interventions | Laparoscopic myomectomy or myomectomy at laparotomy | |
| Outcomes | Surgical outcomes: 1‐ mean operative time 2‐ average postoperative drop in haemoglobin 3‐ Incidence of postoperative pyrexia 4‐ average postoperative hospital stay. Fertility outcomes: 1‐ clinical pregnancy rate 2‐ miscarriage rate 3‐ ongoing clinical pregnancy 4‐ preterm delivery rate 5‐ caesarean section rate. |
|
| Notes | No power calculation Follow‐up period: authors allowed for 6 months after surgical resection before trying for pregnancy. After this, authors state a minimum follow‐up period of 12 months. (Group 1 mean: 32.4+/‐18.5 months, Group 2: 30.6+/‐16.9 months) Funding: none stated Conflict of interest: none stated Study dates: 1991‐1998 Trial registration number: unknown |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation by random number generation |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding of participants and personnel (Performance bias) All outcomes | Low risk | Due to the nature of the intervention, personnel could not be blinded. Furthermore, participants could not be blinded as surgical scars varied between interventions. Therefore, performance bias was not considered a source of bias in this study, |
| Blinding of outcome assessors (Detection bias) All outcomes | Unclear risk | It remains unclear whether outcome assessors were blinded when analysing results (detection bias) |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Outcomes reported for all patients who started the study |
| Selective reporting (reporting bias) | Low risk | All specified outcomes reported in the results section |
| Other bias | Low risk | No evidence of other bias |
FSH: follicle stimulating hormone; IM: intramural; SM: submucous; SS: subserous.
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Bernard 2000 | Retrospective observational study |
| Bulletti 1999 | Prospective observational study |
| Bulletti 2004 | Non randomised study |
| Campo 2003 | Prospective observational study |
| Chang 2011 | 1‐ Non‐randomised study 2‐ Infertility not an inclusion criterion |
| Chatterjee 2012 | Retrospective observational study |
| Chong 1988 | Retrospective observational study |
| Darai 1997 | Retrospective observational study |
| Dubuisson 2000 | Retrospective observational study |
| Fauconnier 2000 | Retrospective observational study |
| Fernandez 2001 | Retrospective observational study |
| Gatti 1989 | Retrospective observational study |
| Gehlbach 1993 | Retrospective observational study |
| Giatras 1999 | Retrospective observational study |
| Kim 2013 | Retrospective observational study |
| Kramer 2016 | Randomised controlled trial but intervention assessed is not within the scope of this review |
| Li 1999 | Retrospective observational study |
| Litta 2014 | Retrospective observational study |
| Malzoni 2003 | Retrospective observational study |
| Narayan 1994 | Retrospective observational study |
| Ribeiro 1999 | Retrospective observational study |
| Rossetti 2001 | Retrospective observational study |
| Saleh 2018 | Prospective observational study |
| Sato 2018 | Conference abstract Retrospective observational study |
| Seyam 2015 | Prospective controlled study, not randomised |
| Shokeir 2010 | This article was retracted in 2011 by the editors of Fertility and Sterility as it duplicates parts of a paper in Hum Reprod 2005;20:1632‐5 |
| Spies 2010 | Prospective study not randomised |
| Sudik 1996 | Comparative retrospective non‐randomised study |
| Ubaldi 1995 | Retrospective observational study |
| Varasteh 1999 | Retrospective observational study |
| Vercellini 1999a | Retrospective observational study |
| Vercellini 1999b | Retrospective observational study |
| Wang 2013 | Prospective uncontrolled study |
| Wang 2016 | Retrospective observational study |
| Wen 2018 | Prospective study not randomised |
| Yarali 2002 | Retrospective observational study |
Characteristics of ongoing studies [ordered by study ID]
NCT03143114.
| Trial name or title | Effect of myomectomy for intramural myoma on fertility outcomes in infertile women |
| Methods | Randomised controlled trial |
| Participants | 100 participants (estimated) Criteria Inclusion Criteria: Infertility for at least one year. Presence of intramural myoma. Absence of any other cause of infertility as revealed by basic infertility work up including laparoscopy. Exclusion Criteria: Age is < 20 or > 33 years. Symptomatic fibroid causing pelviabdominal swelling. Presence of > 2 myomas. Presence of a coexisting another type of myoma other than intramural myoma (e.g. submucosal, subserosal, cervical or ligamentary myoma). Presence of any other cause of infertility. |
| Interventions | Group 1: Myomectomy by laparotomy Group 2: Conservative management |
| Outcomes | Primary outcome: Clinical pregnancy rate [Time Frame: 6‐8 weeks gestational age] Number of clinical pregnancies (defined as presence of at least one intrauterine gestational sac with fetal pole and cardiac activity on TVS scan at 6‐8 weeks gestational age) divided by the number of women Secondary outcome: Miscarriage rate [Time Frame: 12 weeks gestational age] Number of first trimester miscarriages (before 12 weeks gestational age) divided by the number of clinical pregnancies |
| Starting date | First posted 8 May 2017 Last updated 30 October 2018 |
| Contact information | wrefaie@yahoo.com |
| Notes |
https://clinicaltrials.gov/show/NCT03143114 Authors were contacted regarding preliminary data but no response was received |
NCT03796130.
| Trial name or title | Does myomectomy for intramural fibroid improve ART outcome? |
| Methods | Randomised controlled trial |
| Participants | 80 participants (estimated) This study will include women who have intramural myomas ranging from 3‐5 cm |
| Interventions | Group 1: Myomectomy will be performed before ART Group 2: Women will have their trial of ART without myomectomy |
| Outcomes | Primary outcome: Ongoing pregnancy rate [Time Frame: 3 months after embryo transfer] Secondary outcomes:
|
| Starting date | 01/12/19 |
| Contact information | eman_elgindy2013@hotmail.com |
| Notes |
https://clinicaltrials.gov/show/NCT03796130 Authors were contacted regarding preliminary data but no response was received |
ART: assisted reproductive technology
Differences between protocol and review
Primary and secondary outcome measures have been updated and modified. In the previous review, only one primary outcome existed (Primary effectiveness measure: Live birth rate). Preterm delivery rate was promoted from a secondary outcome to a primary outcome as the primary safety measure as it is the leading cause of neonatal mortality. Secondary outcomes are clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, clinical pregnancy rate and caesarean section. Methods sections have been updated to reflect Cochrane Gynaecology and Fertility policy such as ensuring the denominator for the primary analyses is per woman randomised.
Contributions of authors
GR and MM extracted and entered the data and wrote the review. AH and YC acted as review authors. Both AH and YC proof‐read and commented on the review.
Sources of support
Internal sources
None, Other.
External sources
None, Other.
Declarations of interest
MM, GR, and YC declare no known conflicts of interest. AH has received grant funding from the MRC, NIHR, CSO, Wellbeing of Women, Roche Diagnostics, Astra Zeneca and Ferring, and is Chair of RCOG Academic Board, ESHRE National Representative for the UK, WES Ambassador, SEUD Board Member, Past Chair of ESHRE Special Interest Group Endometriosis, Member of NICE and ESHRE Endometriosis Guideline Groups, Trustee and Medical Advisor to Endometriosis UK, Medical Advisor to Pelvic Pain Support Network, and Deputy Editor in chief of Human Reproduction Open. AH's institution has received consultancy fees from Roche Diagnostics, AbbVie, Nordic Pharma and Ferring for work carried out on their behalf.
New search for studies and content updated (no change to conclusions)
References
References to studies included in this review
Casini 2006 {published data only}
- Casini ML, Rossi F, Agostini R, Unfer V. Effects of the position of fibroids on fertility. Gynecological Endocrinology 2006;22(2):106‐9. [DOI] [PubMed] [Google Scholar]
Palomba 2007 {published data only}
- Palomba S, Zupi E, Falbo A, Russo T, Marconi D, Tolino A, et al. A multicenter randomized, controlled study comparing laparoscopic versus minilaparotomic myomectomy: reproductive outcomes. Fertility and Sterility 2007;88(4):933–41. [DOI] [PubMed] [Google Scholar]
Roy 2017 {published data only}
- Roy KK, Metta S, Kansal Y, Kumar S, Singhal S, Vanamail P. A prospective randomized study comparing unipolar versus bipolar hysteroscopic myomectomy in infertile women. Journal of Human Reproductive Sciences 2017;10(3):185‐93. [DOI] [PMC free article] [PubMed] [Google Scholar]
Seracchioli 2000 {published data only}
- Seracchioli R, Rossi S, Govoni F, Rossi E, Venturoli S, Bulletti C, et al. Fertility and obstetric outcome after laparoscopic myomectomy of large myomata: a randomized comparison with abdominal delivery. Human Reproduction 2000;15(12):2663‐8. [DOI] [PubMed] [Google Scholar]
References to studies excluded from this review
Bernard 2000 {published data only}
- Bernard G, Darai E, Poncelet C, Benifla JL, Madelenat P. Fertility after hysteroscopic myomectomy: effect of intramural myomas associated. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2000;88:85‐90. [DOI] [PubMed] [Google Scholar]
Bulletti 1999 {published data only}
- Bulletti C, Ziegler D, Polli V, Flamigni C. The role of leiomyomas in infertility. Journal of the American Association of Gynaecologic Laparoscopists 1999;6(4):441‐5. [DOI] [PubMed] [Google Scholar]
Bulletti 2004 {published data only}
- Bulletti C, Ziegler D, Levi Setti P, Cicinelli E, Polli V, Stefanetti M. Myomas, pregnancy outcome, and in vitro fertilization. Annals of the New York Academy of Sciences 2004;1034:84‐92. [DOI] [PubMed] [Google Scholar]
Campo 2003 {published data only}
- Campo S, Campo V, Gambadauro P. Reproductive outcome before and after laparoscopic or abdominal myomectomy for subserous intramural myomas. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2003;110:215‐9. [DOI] [PubMed] [Google Scholar]
Chang 2011 {published data only}
- Chang WC, Chou LY, Chang DY, Huang PS, Huang SC, Chen SY, et al. Simultaneous laparoscopic uterine artery ligation and laparoscopic myomectomy for symptomatic uterine myomas with and without in situ morcellation. Human Reproduction 2011;26(7):1735‐40. [DOI] [PubMed] [Google Scholar]
Chatterjee 2012 {published data only}
- Chatterjee S, Chatterjee A, Chowdhury R, Dey S, Ganguly D. Fertility promoting laparoscopic surgery: our experience. Journal of South Asian Federation of Obstetrics and Gynaecology 2012;4:12‐6. [Google Scholar]
Chong 1988 {published data only}
- Chong RK, Thong PH, Tan SL, Thong P, Salmon YM. Myomectomy: Indications, results of surgery and relation to fertility. Singapore Medical Journal 1988;29:35‐7. [PubMed] [Google Scholar]
Darai 1997 {published data only}
- Darai E, Dechaud H, Benifla JL, Renolleau C, Panel P, Madelenat P. Fertility after laparoscopic myomectomy: preliminary results. Human Reproduction 1997;12(9):1931‐4. [DOI] [PubMed] [Google Scholar]
Dubuisson 2000 {published data only}
- Dubuisson JB, Fauconnier A, Chapron C, Kreiker G, Norgaard C. Reproductive outcome after laparoscopic myomectomy in infertile women. Journal of Reproductive Medicine 2000;45(1):23‐30. [PubMed] [Google Scholar]
Fauconnier 2000 {published data only}
- Fauconnier A, Dubuisson J, Ancel P, Chapron C. Prognostic factors of reproductive outcome after myomectomy in infertile patients. Human Reproduction 2000;15(8):1751‐7. [DOI] [PubMed] [Google Scholar]
Fernandez 2001 {published data only}
- Fernandez H, Sefrioui O, Virelizier C, Gervaise A, Gomel V, Frydman R. Hysteroscopic resection of submucosal myomas in patients with infertility. Human Reproduction 2001;16(7):1489‐92. [DOI] [PubMed] [Google Scholar]
Gatti 1989 {published data only}
- Gatti D, Falsetti L, Viani A, Gastaldi A. Uterine fibromyoma and sterility: role of myomectomy. Acta Europaea Fertilitatis 1989;20(1):11‐3. [PubMed] [Google Scholar]
Gehlbach 1993 {published data only}
- Gehlbach DL, Sousa RC, Carpeter SE, Rock JA. Abdominal myomectomy in the treatment of infertility. International Journal of Gynaecology and Obstetrics 1993;40(1):45‐50. [DOI] [PubMed] [Google Scholar]
Giatras 1999 {published data only}
- Giatras K, Berkeley AS, Noyes N, Licciardi F, Lolis D, Grifo JA. Fertility after hysteroscopic resection of submucous myomas. Journal of the American Association of Gynecologic Laparoscopists 1999;6(2):155‐8. [DOI] [PubMed] [Google Scholar]
Kim 2013 {published data only}
- Kim M, Uhm Y, Kim J, Jee B, Kim Y. Obstetric outcomes after uterine myomectomy: Laparoscopic versus laparotomic approach. Obstetrics and Gynecology Science 2013;56:375‐81. [DOI] [PMC free article] [PubMed] [Google Scholar]
Kramer 2016 {published data only}
- Krämer B, Hahn M, Taran F, Kraemer D, Isaacson KB, Brucker SY. Interim analysis of a randomized controlled trial comparing laparoscopic radiofrequency volumetric thermal ablation of uterine fibroids with laparoscopic myomectomy.. International Journal of Gynecology and Obstetrics 2016;133:206‐11. [DOI] [PubMed] [Google Scholar]
Li 1999 {published data only}
- Li TC, Mortimer R, Cooke ID. Myomectomy: a retrospective study to examine reproductive performance before and after surgery. Human Reproduction 1999;14(7):1735‐40. [DOI] [PubMed] [Google Scholar]
Litta 2014 {published data only}
- Litta P, Conte L, Marchi F, Saccardi C, Angioni S. Pregnancy outcome after hysteroscopic myomectomy. Gynecological Endocrinology 2014;30(2):149‐52. [DOI] [PubMed] [Google Scholar]
Malzoni 2003 {published data only}
- Malzoni M, Rotondi M, Perone C, Labriola D, Ammaturo F, Izzo A, et al. Fertility after laparoscopic myomectomy of large uterine myomas: operative technique and preliminary results. European Journal of Gynaecological Oncology 2003;24(1):79‐82. [PubMed] [Google Scholar]
Narayan 1994 {published data only}
- Narayan R, Goswamy K. Treatment of submucous fibroids, and the outcome of assisted conception. Journal of the American Association of Gynecologic Laparoscopists 1994;1(4 pt 1):307‐11. [DOI] [PubMed] [Google Scholar]
Ribeiro 1999 {published data only}
- Ribeiro SC, Reich H, Rosenberg J, Guglielminetti E, Vidali A. Laparoscopic myomectomy and pregnancy outcome in infertile patients. Fertility and Sterility 1999;71(3):571‐4. [DOI] [PubMed] [Google Scholar]
Rossetti 2001 {published data only}
- Rossetti A, Sizzi O, Soranna L, Lanzone A. Fertility outcome: long term results after laparoscopic myomectomy. Gynecological Endocrinology 2001;15:129‐34. [PubMed] [Google Scholar]
Saleh 2018 {published data only}
- Saleh HS, Mowafy HE, Hameid AA, Sherif HE, Mahfouz E.M. Does uterine fibroid adversely affect obstetric outcome of pregnancy?. BioMed Research International 2018;2018:1‐5. [DOI] [PMC free article] [PubMed] [Google Scholar]
Sato 2018 {published data only}
- Sato M, Hara S, Suyama F, Beck W, Mukoda Y. Impact of laparoscopic myomectomy on reproductive and obstetric outcomes in patients with intramural myomas. Human Reproduction 2018;33:478‐9. [Google Scholar]
Seyam 2015 {published data only}
- Seyam E, Hassan M, Gad M, Mahmoud H, Ibrahum M. Pregnancy outcome after office microhysteroscopy in women with unexplained infertility. International Journal of Fertility and Sterility 2015;9:168‐75. [DOI] [PMC free article] [PubMed] [Google Scholar]
Shokeir 2010 {published data only}
- Shokeir T, El‐Shafei M, Yousef H, Allam AF, Sadek E. Submucous myomas and their implications in the pregnancy rates of patients with otherwise unexplained primary infertility undergoing hysteroscopic myomectomy: a randomized matched control study. Fertility and Sterility 2010;94(2):724‐9. [DOI] [PubMed] [Google Scholar]
Spies 2010 {published data only}
- Spies J, Bradley L, Guido R, Maxwell L, Levine B, Coyne K. Outcomes from leiomyoma therapies. Obstetrics and Gynecology 2010;116(3):641‐52. [DOI] [PubMed] [Google Scholar]
Sudik 1996 {published data only}
- Sudik R, Husch K, Stellar J, Daume E. Fertility and pregnancy outcome after myomectomy in sterility patients. European Journal of Obstetrics, Gynecology, and Reproductive Biology 1996;65:209‐14. [DOI] [PubMed] [Google Scholar]
Ubaldi 1995 {published data only}
- Ubaldi F, Tournaye H, Camus M, Pas H, Gepts E, Devroey P. Fertility after hysteroscopic myomectomy. Human Reproduction Update 1995;1(1):81‐90. [DOI] [PubMed] [Google Scholar]
Varasteh 1999 {published data only}
- Varasteh NN, Varasteh RS, Neuwirth BL, Keltz MD. Pregnancy rates after hysteroscopic polypectomy and myomectomy in infertile women. Obstetrics and Gynecology 1999;94(2):168‐71. [DOI] [PubMed] [Google Scholar]
Vercellini 1999a {published data only}
- Vercellini P, Zaina B, Yaylayan L, Pisacreta A, Giorgio O, Crosignani PG. Hysteroscopic myomectomy: Long term effect on menstrual pattern and fertility. Obstetrics and Gynecology 1999;94(3):341‐7. [DOI] [PubMed] [Google Scholar]
Vercellini 1999b {published data only}
- Vercellini P, Maddalena S, Giorgi O, Pesole A, Ferrari L, Crosignani PG. Determinants of reproductive outcome after abdominal myomectomy for infertility. Fertility and Sterility 1999;72(1):109‐14. [DOI] [PubMed] [Google Scholar]
Wang 2013 {published data only}
- Wang CJ, Yu HT, Wu PJ, Su H, Wu KY, Han CM. Laparoscopic myomectomy instead of hysteroscopic myomectomy for large submucous fibroids. Gynecology and Minimally Invasive Therapy 2013;2:93‐5. [Google Scholar]
Wang 2016 {published data only}
- Wang H, Zhao J, Li X, Li P, Lu C, Tian S, Wang ZH. The indication and curative effect of hysteroscopic and laparoscopic myomectomy for type II submucous myomas. BMC Surgery 2016;16(9):1‐7. [DOI] [PMC free article] [PubMed] [Google Scholar]
Wen 2018 {published data only}
- Wen KC, Sung PL, Chang WH, Horng HC, Chen YJ, Lee WL, et al. A case‐control study to compare the outcome of women treated by two minimally invasive procedures‐ ultraminilaparotomy myomectomy and laparoscopic myomectomy. Taiwanese Journal of Obstetrics and Gynecology 2018;57:264‐9. [DOI] [PubMed] [Google Scholar]
Yarali 2002 {published data only}
- Yarali H, Bukulmez O. The effect of intramural and subserous uterine fibroids on implantation and clinical pregnancy rates in patients having intracytoplasmic sperm injection. Archives of Gynecology and Obstetrics 2002;266:30‐3. [DOI] [PubMed] [Google Scholar]
References to ongoing studies
NCT03143114 {unpublished data only}
- NCT03143114. Effect of myomectomy for intramural myoma on fertility outcomes in infertile women [Effect of myomectomy for intramural myoma on fertility outcomes in infertile women: a randomized clinical trial]. clinicaltrials.gov/ct2/show/NCT03143114 (first received 8 May 2017).
NCT03796130 {unpublished data only}
- NCT03796130. Does myomectomy for intramural fibroid improve ART outcome? (MIFART) [Does myomectomy for intramural fibroid improve ART outcome? A randomized controlled trial]. clinicaltrials.gov/ct2/show/NCT03796130 (first received 8 January 2019).
Additional references
Chamberlain 2003
- Chamberlain G. The master of myomectomy. Journal of the Royal Society of Medicine 2003;96(6):302‐4. [DOI] [PMC free article] [PubMed] [Google Scholar]
Dubuisso 2000
- Dubuisso JB, Fauconnier A, Babaki‐Fard K, Chapron C. Laparoscopic myomectomy: a current view. Human Reproduction Update 2000;6(6):588‐94. [DOI] [PubMed] [Google Scholar]
Emanuel 1997
- Emanuel M, Hart A, Wamsteker K, Lammes F. An analysis of fluid loss during transcervical resection of submucous myomas. Fertility and Sterility 1997;68:881‐6. [DOI] [PubMed] [Google Scholar]
Farquhar 2009
- Farquhar C. Do uterine fibroids cause infertility and should they be removed to increase fertility?. BMJ 2009;16:338. [DOI] [PubMed] [Google Scholar]
GRADEpro GDT 2015 [Computer program]
- GRADEpro GDT. GRADEpro Guideline Development Tool [Software]. MxMaster University: Evidence Prime, Inc.. McMaster University: Evidence Prime, Inc., 2015.
Gupta 2014
- Gupta JK, Sinha A, Lumsden MA, Hickey M. Uterine artery embolization for symptomatic uterine fibroids. Cochrane Database of Systematic Reviews 2014, Issue 12. [DOI: 10.1002/14651858.CD005073.pub4] [DOI] [PMC free article] [PubMed] [Google Scholar]
Hall 2015
- Hall T, Lee S, Boruta D, Goodman A. Medical device safety and surgical dissemination of unrecognized uterine malignancy: morcellation in minimally invasive gynecologic surgery. Oncologist 2015;20(11):1274‐82. [DOI] [PMC free article] [PubMed] [Google Scholar]
Hallez 1995
- Hallez JP. Single‐stage total hysteroscopic myomectomies: indications, techniques, and results. Fertility and Sterility 1995;63:703‐8. [PubMed] [Google Scholar]
Higgins 2011
- Higgins JP, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Inagaki 2003
- Inagaki N, Ung L, Otani T, Wilkinson D, Lopata A. Uterine cavity matrix metalloproteinases and cytokines in patients with leiomyoma, adenomyosis or endometrial polyp. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2003;111:197‐203. [DOI] [PubMed] [Google Scholar]
Kadam 2010
- Kadam P, Bhalerao S. Sample size calculation. International Journal of Ayurveda Research 2010;1(1):55‐7. [DOI] [PMC free article] [PubMed] [Google Scholar]
Klatsky 2008
- Klatsky PC, Tran ND, Caughey AB, Fujimoto VY. Fibroids and reproductive outcomes: a systematic review from conception to delivery. American Journal of Obstetrics and Gynecology 2008;198(4):357–66. [DOI] [PubMed] [Google Scholar]
Kroon 2011
- Kroon B, Johnson N, Chapman M, Yazdani A, Hart R, Australasian CREI Consensus Expert Panel on Trial evidence (ACCEPT) group. Fibroids in infertility‐‐consensus statement from ACCEPT (Australasian CREI Consensus Expert Panel on Trial evidence). The Australian & New Zealand Journal of Obstetrics & Gynaecology 2011;51(4):289‐95. [DOI] [PubMed] [Google Scholar]
Litta 2014a
- Liita P, Conte L, Marchi F, Saccardi C, Angioni S. Pregnancy outcome after hysteroscopic myomectomy. Gynecological Endocrinology 2014;30:149‐52. [DOI] [PubMed] [Google Scholar]
Litta 2014b
- Liita P, Leggieri C, Conte L, Dalla Toffola A, Multinu F, Angioni S. Monopolar versus bipolar device: Safety, feasibility, limits and perioperative complications in performing hysteroscopic myomectomy. Clinical and Experiemental Obstetrics & Gynecology 2014;41:335‐338. [PubMed] [Google Scholar]
Makris 2007
- Makris N, Vomvolaki E, Mantzaris G, Kalmantis K, Hatzipappas J, Antsaklis A. Role of bipolar rectoscope in subfertile women with submucous myomas and menstrual disorders. Journal of Obstetrics and Gynaecology Research 2007;33:849‐54. [DOI] [PubMed] [Google Scholar]
Metwally 2011
- Metwally M, Farquhar CM, Li TC. Is another meta‐analysis on the effects of intramural fibroids on reproductive outcomes needed?. Reproductive Biomedicine Online 2011;23(1):2‐14. [DOI] [PubMed] [Google Scholar]
Metwally 2015
- Metwally M, Li TC. Reproductive Surgery in Assisted Conception. Springer, 2015. [Google Scholar]
Office for National Statistics 2019
- Office for National Statistics. Birth characteristics in England and Wales: 2017. Office for National Statistics 2019.
Pritts 2009
- Pritts EA, Parker WH, Olive DL. Fibroids and infertility: an updated systematic review of the evidence. Fertility and Sterility 2009;91(4):1215‐23. [DOI] [PubMed] [Google Scholar]
Sardo 2008
- Sardo ADS, Mazzon I, Bramante S, Bettocchi S, Bifulco G, Guida M. Hysteroscopic myomectomy: a comprehensive review of surgical techniques. Human Reproduction Update 2008;14:101‐19. [DOI] [PubMed] [Google Scholar]
Somigliana 2007
- Somigliana E, Vercellini P, Daguati R, Pasin R, Giorgi O, Crosignani PG. Fibroids and female reproduction: a critical analysis of the evidence. Human Reproduction Update 2007;13(5):456‐76. [DOI] [PubMed] [Google Scholar]
Sunkara 2010
- Sunkara SK, Khairy M, El‐Toukhy T, Khalaf Y, Coomarasamy A. The effect of intramural fibroids without uterine cavity involvement on the outcome of IVF treatment: a systematic review and meta‐analysis. Human Reproduction 2010;25(2):418‐29. [DOI] [PubMed] [Google Scholar]
Wechter 2011
- Wechter M, Stewart E, Myers E, Kho R, Wu J. Leiomyoma‐related hospitalization and surgery: Prevalence and predicted growth based on population trends. American Journal of Obstetrics and Gynecology 2011;205:492.e1‐492.e5. [DOI] [PMC free article] [PubMed] [Google Scholar]
Yoshino 2010
- Yoshino O, Hayashi T, Osuga Y, Orisaka M, Asada H, Okuda S, et al. Decreased pregnancy rate is linked to abnormal uterine peristalsis caused by intramural fibroids. Human Reproduction 2010;25(10):2475‐9. [DOI] [PubMed] [Google Scholar]
Yoshino 2012
- Yoshino O, Nishii O, Osuga Y, Asada H, Okuda S, Orisaka M, et al. Myomectomy decreases abnormal uterine peristalsis and increases pregnancy rate. Journal of Minimally Invasive Gynecology 2012;19(1):63‐7. [DOI] [PubMed] [Google Scholar]
References to other published versions of this review
Griffiths 2002
- Griffiths AN, D'Angelo A, Amso NN. Surgical treatment of fibroids for subfertility. Cochrane Database of Systematic Reviews 2002, Issue 3. [DOI: 10.1002/14651858.CD003857] [DOI] [PubMed] [Google Scholar]
Griffiths 2006
- Griffiths AN, D'Angelo A, Amso NN. Surgical treatment of fibroids for subfertility. Cochrane Database of Systematic Reviews 2006, Issue 3. [DOI: 10.1002/14651858.CD003857.pub2] [DOI] [PubMed] [Google Scholar]
Metwally 2012
- Metwally M, Cheong YC, Horne AW. Surgical treatment of fibroids for subfertility. Cochrane Database of Systematic Reviews 2012, Issue 11. [DOI: 10.1002/14651858.CD003857.pub3] [DOI] [PubMed] [Google Scholar]