Laparoscopic surgery for presumed benign ovarian tumor during pregnancy

Abstract

Background

The surgical management of ovarian tumors in pregnancy is similar to that of non‐pregnant women. The procedures include resection of the tumor (enucleation), removal of an ovary or ovaries (oophorectomy), or surgical excision of the fallopian tube and ovary (salpingo‐oophorectomy). The procedure can be done by open surgery (laparotomy) or keyhole surgery (laparoscopy) technique. The benefits of laparoscopic surgery include shorter hospital stay, earlier return to normal activity, and reduced postoperative pain. However, conventional laparoscopic surgery techniques required the infusion of gas carbon dioxide in the peritoneum to distend the abdomen and displace the bowel upward to create the room for surgical manipulation. Serious complications such as abnormally high levels of carbon dioxide in the circulating blood (hypercarbia) and perforation of internal organs have also been reported. These serious complication may be harmful to the fetus.

Objectives

To compare the effects of using laparoscopic surgery for benign ovarian tumor during pregnancy on maternal and fetal health and the use of healthcare resources.

Search methods

We updated the search of the Cochrane Pregnancy and Childbirth Group's Trials Register on 11 November 2012.

Selection criteria

Randomized controlled trials with reported data that compared outcomes of laparoscopic surgery for benign ovarian tumor in pregnancy to conventional laparotomy technique.

Data collection and analysis

Two review authors planned to independently assess trial quality and extract data.

Main results

The updated search did not identify any randomized controlled trials.

Authors' conclusions

The practice of laparoscopic surgery for benign ovarian tumour during pregnancy is associated with benefits and harms. However, the evidence for the magnitude of these benefits and harms is drawn from case series studies, associated with potential bias. The results and conclusions of these studies must therefore be interpreted with caution.

The available case series studies of laparoscopic surgery for benign ovarian tumour during pregnancy provide limited insight into the potential benefits and harms associated with this new surgical technique in pregnancy. Randomized controlled trials are required to provide the most reliable evidence regarding the benefits and harms of laparoscopic surgery for benign ovarian tumour during pregnancy.

Plain language summary

Laparoscopic surgery for presumed benign ovarian tumor during pregnancy

No randomized controlled trials to compare 'open surgery' with 'keyhole surgery' in pregnant women for non‐malignant tumors of the ovary.

A small number of women have tumors of the ovaries diagnosed during pregnancy. Most of these tumors are not malignant, and if they are small then treatment can be left until after the birth. However, if the tumour is larger that 6 cm in diameter, it is suggested that it is better to operate and remove them during pregnancy, as they may interfere with the birth of the baby. Surgical procedures for these non‐malignant tumors of the ovary in pregnancy can be performed by open surgery (laparotomy) or keyhole surgery (laparoscopy) techniques. Historically, open surgery has been used, but new keyhole surgery seems attractive in that it appears to require a shorter hospital stay and there is a quicker return to normal activities for women. However, the infusion of gas into the abdomen during the key‐hole procedure may have adverse effects on the baby, and an additional gasless technique is also under study. This review aimed to address the question of which surgical technique might be better as all have benefits and risks to the mother and the baby. There were no randomized controlled trials identified that compared the effects of using keyhole surgery for benign tumors of the ovary during pregnancy on maternal and fetal health. There was some evidence available from case series studies, but more research is needed on the potential benefits and harms associated with this new surgical technique in pregnancy.

Background

Ultrasound scanning during early pregnancy has increased the number of ovarian tumors identified. The ovarian tumor can be classified as benign or malignant. During pregnancy, ovarian tumors are mostly benign. Most women present with the problem of discrepancy between the uterine size and gestational age, palpable mass, and abdominal pain. The serous cystadenoma and dermoid cyst are the two most common pathologies found (Hess 1988; Jacob 1990). Ovarian tumor in pregnancy requiring surgical intervention has an incidence ranging from 0.0004% to 0.36% (Graber 1974; Sherard 2003; Wang 1999). The surgical procedure is similar to that of non‐pregnant women. Elective surgical removal is recommended for any mass larger than 6 cm in diameter that continues to exist into the second trimester, unless the mass is suspected to be a uterine fibroid (leiomyoma) (Hess 1988). There are the risks of torsion, rupture or leakage of the cysts as pregnancy advances.

The surgical treatment performed is resection of the tumor (enucleation), removal of an ovary or ovaries (oophorectomy), or surgical excision of the fallopian tube and ovary (salpingo‐oophorectomy). The surgery can be done by open surgery (laparotomy) or keyhole surgery (laparoscopy) technique (Pittaway 1994). Laparoscopic surgery involves using an endoscope inserted into or through the abdominal wall to view abdominal, or pelvic organs, or both, while operating with instruments introduced through separate small incisions.

Laparoscopic surgery has been extensively used as a treatment for many diseases. It has been performed successfully in pregnancy for many conditions, for example removal of the gallbladder (cholecystectomy) (Pucci 1991; Soper 1992), removal of the appendix (appendectomy) (Schreiber 1990), and ovarian torsion (Lang 1992; Shalev 1990). In case of suspected malignant ovarian tumor, the laparoscopic surgery should be avoided due to the risk of port site metastasis and inadequate surgical staging (Agostini 2002; Morice 2000; Morice 2004).

The benefits of laparoscopic surgery include shorter hospital stay, earlier return to normal activity, and reduced postoperative pain (Mais 1995). However, conventional laparoscopic surgery techniques required the infusion of gas carbon dioxide in the peritoneum to distend the abdomen and displace the bowel upward to create the room for surgical manipulation. Serious complications such as hypercarbia and perforation of internal organs have also been reported. Many reports recommend clinicians avoid using the gas carbon dioxide to inflate the abdomen, as animal studies suggest that it increases intra‐abdominal pressure which leads to the decrease of the uterine blood flow which can be hazardous to the fetus (Jansen 1979). A further animal study confirmed this finding and reported decreased uterine blood flow from using the gas carbon dioxide pneumoperitoneum (Curet 1996). Thus, the new method of the gasless laparoscopic technique has been suggested (Akira 1999; Bunyavejchevin 2007).

Since the 1990s, there have been many reports exploring the relative merits and potential risks of laparoscopic surgery for benign ovarian tumors in pregnancy (Lin 2003; Nezhat 1991; Yamada 2004). Evidence for the safety of the laparoscopic technique during pregnancy has not been fully evaluated.

Objectives

To compare the effects of using laparoscopic surgery for benign ovarian tumor during pregnancy on maternal and fetal health and the use of healthcare resources.

Methods

Criteria for considering studies for this review

Types of studies

Randomized controlled trials examining laparoscopic surgery for benign ovarian tumor in pregnancy compared to conventional laparotomy technique.

Types of participants

Women with benign ovarian tumor during pregnancy.

Types of interventions

Randomized allocation of women with benign ovarian tumor in pregnancy to laparoscopic surgery or conventional laparotomy technique.

Types of outcome measures

Primary outcomes

Maternal complications: wound infection, thromboembolism, surgical injury to bladder, ureter, bowel.

Secondary outcomes

Maternal

• Operating time (minutes)

• Intraoperative blood loss

• Recurrent rate: the incidence of second operation due to the reoccurrence of the tumor in the same ovary

• Complications during labor; uterine rupture

• Miscarriage

• Caesarean section

• Postpartum hemorrhage

• Anemia (hematocrit is less than 33%)

• Need for conversion (defined as a procedure initiated as laparoscopic but converted to open, or a procedure initiated as open but converted to laparoscopic)

• Time to return to usual activities (days)

• Rate of adhesion detections

• Pain intensity (during the first three postoperative days)

• Maternal death

• Quality of life assessment

• Participant's acceptability

Neonatal

• Gestational age less than 37 weeks at birth

• Gestational age at birth

• Apgar score (less than seven at five minutes)

• Low cord pH

• Intubation required

• Use of mechanical ventilation

• Seizures

• Infection

• Jaundice

• Intracranial pathology

• Perinatal death

Use of health service resources

• For the woman: length of postoperative hospital stay, re‐admission to hospital

• For the infant: admission to special care

Search methods for identification of studies

Electronic searches

We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register by contacting the Trials Search Co‐ordinator (11 November 2012). 

The Cochrane Pregnancy and Childbirth Group’s Trials Register is maintained by the Trials Search Co‐ordinator and contains trials identified from: 

1. monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);

2. weekly searches of MEDLINE;

3. weekly searches of EMBASE;

4. handsearches of 30 journals and the proceedings of major conferences;

5. weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts.

Details of the search strategies for CENTRAL, MEDLINE and EMBASE, the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service can be found in the ‘Specialized Register’ section within the editorial information about the Cochrane Pregnancy and Childbirth Group. 

Trials identified through the searching activities described above are each assigned to a review topic (or topics). The Trials Search Co‐ordinator searches the register for each review using the topic list rather than keywords. 

We did not apply any language restrictions.

Data collection and analysis

Selection of studies

Two review authors (S Bunyavejchevin (SB) and V Phupong (VP)) planned to independently assess for inclusion all the potential studies we identified as a result of the search strategy. We planned to resolve any disagreement through discussion or, if required, consult a third person.

Data extraction and management

We planned to design a form to extract data. For eligible studies, two review authors planned to extract the data using the agreed form. We planned to resolve discrepancies through discussion or, if required, consult a third person. We planned to enter data into Review Manager software (RevMan 2011) and check for accuracy.

When information regarding any of the above is unclear, we planned to attempt to contact authors of the original reports to provide further details.

Assessment of risk of bias in included studies

Two review authors planned to independently assess risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We planned to resolve any disagreement by discussion or by involving a third assessor.

(1) Random sequence generation (checking for possible selection bias)

We planned to describe for each included study the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.

We planned to assess the method as:

• low risk of bias (any truly random process, e.g. random number table; computer random number generator);

• high risk of bias (any non‐random process, e.g. odd or even date of birth; hospital or clinic record number); or

• unclear risk of bias.   

(2) Allocation concealment (checking for possible selection bias)

We planned to describe for each included study the method used to conceal allocation to interventions prior to assignment and will assess whether intervention allocation could have been foreseen in advance of, or during recruitment, or changed after assignment.

We planned to assess the methods as:

• low risk of bias (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes);

• high risk of bias (open random allocation; unsealed or non‐opaque envelopes, alternation; date of birth);

• unclear risk of bias.   

(3.1) Blinding of participants and personnel (checking for possible performance bias)

We planned to describe for each included study the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. We planned to consider that studies are at low risk of bias if they were blinded, or if we judge that the lack of blinding would be unlikely to affect results. We planned to assess blinding separately for different outcomes or classes of outcomes.

We planned to assess the methods as:

• low, high or unclear risk of bias for participants;

• low, high or unclear risk of bias for personnel.

(3.2) Blinding of outcome assessment (checking for possible detection bias)

We planned to describe for each included study the methods used, if any, to blind outcome assessors from knowledge of which intervention a participant received.  We planned to assess blinding separately for different outcomes or classes of outcomes.

We planned to assess methods used to blind outcome assessment as:

• low, high or unclear risk of bias.

(4) Incomplete outcome data (checking for possible attrition bias due to the amount, nature and handling of incomplete outcome data)

We planned to describe for each included study, and for each outcome or class of outcomes, the completeness of data including attrition and exclusions from the analysis. We planned to state whether attrition and exclusions were reported and the numbers included in the analysis at each stage (compared with the total randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes.  Where sufficient information is reported, or can be supplied by the trial authors, we planned to re‐include missing data in the analyses which we undertake.

We planned to assess methods as:

• low risk of bias (e.g. no missing outcome data; missing outcome data balanced across groups);

• high risk of bias (e.g. numbers or reasons for missing data imbalanced across groups; ‘as treated’ analysis done with substantial departure of intervention received from that assigned at randomisation);

• unclear risk of bias.

(5) Selective reporting (checking for reporting bias)

We planned to describe for each included study how we investigated the possibility of selective outcome reporting bias and what we found.

We planned to assess the methods as:

• low risk of bias (where it is clear that all of the study’s pre‐specified outcomes and all expected outcomes of interest to the review have been reported);

• high risk of bias (where not all the study’s pre‐specified outcomes have been reported; one or more reported primary outcomes were not pre‐specified; outcomes of interest are reported incompletely and so cannot be used; study fails to include results of a key outcome that would have been expected to have been reported);

• unclear risk of bias.

(6) Other bias (checking for bias due to problems not covered by (1) to (5) above)

We planned to describe for each included study any important concerns we have about other possible sources of bias.

We planned to assess whether each study was free of other problems that could put it at risk of bias:

• low risk of other bias;

• high risk of other bias;

• unclear whether there is risk of other bias.

(7) Overall risk of bias

We planned to make explicit judgements about whether studies are at high risk of bias, according to the criteria given in the Handbook (Higgins 2011). With reference to (1) to (6) above, we planned to assess the likely magnitude and direction of the bias and whether we consider it is likely to impact on the findings.  We planned to explore the impact of the level of bias through undertaking sensitivity analyses ‐ see Sensitivity analysis. 

Measures of treatment effect

Dichotomous data

For dichotomous data, we planned to present results as summary risk ratio with 95% confidence intervals. 

Continuous data

For continuous data, we planned to use the mean difference if outcomes are measured in the same way between trials. We planned to use the standardised mean difference to combine trials that measure the same outcome, but use different methods.  

Dealing with missing data

For included studies, we planned to note levels of attrition. We planned to explore the impact of including studies with high levels of missing data in the overall assessment of treatment effect by using sensitivity analysis.

For all outcomes, we planned to carry out analyses, as far as possible, on an intention‐to‐treat basis, i.e. we planned to attempt to include all participants randomised to each group in the analyses, and all participants will be analysed in the group to which they were allocated, regardless of whether or not they received the allocated intervention. The denominator for each outcome in each trial will be the number randomised minus any participants whose outcomes are known to be missing.

Assessment of heterogeneity

We planned to assess statistical heterogeneity in each meta‐analysis using the T², I² and Chi² statistics. We planned to regard heterogeneity as substantial if I² is greater than 30% and either T² is greater than zero, or there is a low P value (less than 0.10) in the Chi² test for heterogeneity. 

Assessment of reporting biases

If there were 10 or more studies in the meta‐analysis, we planned to investigate reporting biases (such as publication bias) using funnel plots. We planned to assess funnel plot asymmetry visually, and use formal tests for funnel plot asymmetry. For continuous outcomes we planned to use the test proposed by Egger 1997, and for dichotomous outcomes we planned to use the test proposed by Harbord 2006. If asymmetry is detected in any of these tests or is suggested by a visual assessment, we planned to perform exploratory analyses to investigate it.

Data synthesis

We planned to carry out statistical analysis using the Review Manager software (RevMan 2011). We planned to use fixed‐effect meta‐analysis for combining data where it is reasonable to assume that studies are estimating the same underlying treatment effect: i.e. where trials are examining the same intervention, and the trials’ populations and methods are judged sufficiently similar. If there is clinical heterogeneity sufficient to expect that the underlying treatment effects differ between trials, or if substantial statistical heterogeneity is detected, we planned to use random‐effects meta‐analysis to produce an overall summary if an average treatment effect across trials is considered clinically meaningful. The random‐effects summary will be treated as the average range of possible treatment effects and we will discuss the clinical implications of treatment effects differing between trials. If the average treatment effect is not clinically meaningful we will not combine trials.

If we use random‐effects analyses, we planned to present the results as the average treatment effect with 95% confidence intervals, and the estimates of  T² and I².

Subgroup analysis and investigation of heterogeneity

Had we identified substantial heterogeneity, we planned to investigate it using subgroup analyses and sensitivity analyses. We planned to consider whether an overall summary is meaningful, and if it is, use random‐effects analysis to produce it.

We planned to carry out the following subgroup analysis:

1.    gas laparoscopic surgery versus gasless laparoscopic surgery.

Results

Description of studies

There were no randomized controlled trials identified from the search strategy.

Risk of bias in included studies

There were no randomized controlled trials identified from the search strategy.

Effects of interventions

There were no randomized controlled trials identified from the search strategy.

Discussion

There were no randomized controlled trials identified that compared the effects of using laparoscopic surgery for benign ovarian tumor during pregnancy on maternal and fetal health and the use of healthcare resources.

There are risks and benefits for both laparoscopic surgery and laparotomy in pregnancy, current sources of information are limited to only case series reports (Loh 1998; Oguri 2005; Patacchiola 2005).

To confirm the safety of laparoscopic treatment for benign ovarian tumour during pregnancy, there is a need for methodologically rigorous studies to provide direct evidence about the relative benefits and harms of and for laparoscopic surgery for benign ovarian tumor compared to laparotomy in pregnancy. This information is best obtained from randomized controlled trials, as this methodology limits the potential for bias and provides the most reliable evidence regarding the benefits and harms of both forms of surgery.

Authors' conclusions

Implications for practice.

The practice of laparoscopic surgery for benign ovarian tumour during pregnancy are associated with benefits and risks. However, the evidence for the magnitude of these benefits and harms is drawn from case series studies, associated with potential bias. The results and conclusions of these studies must therefore, be interpreted with caution.

Implications for research.

The available case series studies of laparoscopic surgery for the benign ovarian tumour during pregnancy provide limited insight into the potential benefits and harms associated with this new surgical technique in pregnancy. Randomized controlled trials are required to provide the most reliable evidence regarding the benefits and harms of laparoscopy surgery for the benign ovarian tumour during pregnancy. Outcomes of interest could be those listed in this review.

What's new

Date	Event	Description
11 November 2012	New citation required but conclusions have not changed	No new trial reports identified.
11 November 2012	New search has been performed	Search updated.

History

Protocol first published: Issue 3, 2005
 Review first published: Issue 4, 2006

Date	Event	Description
11 September 2008	Amended	Converted to new review format.

Contributions of authors

S Bunyavejchevin: developed the basis of the protocol, performed the background literature search, drafted the protocol and the review, and revised the drafts in response to editorial comments. 
 V Phupong: performed the background literature search, and helped draft the protocol and review.

Sources of support

Internal sources

• Faculty of Medicine, Chulalongkorn University, Thailand.

External sources

• Thai Cochrane Network, Thailand.

Declarations of interest

None known.

New search for studies and content updated (no change to conclusions)