Laparoscopic application of heat or laser to the ovaries to cause ovulation in women with polycystic ovary syndrome who do not ovulate

Review question

Cochrane authors reviewed the evidence about the effect of a surgical procedure called laparoscopic ovarian drilling (LOD) compared with medical treatment to cause ovulation in women with polycystic ovary syndrome (PCOS) who do not ovulate. We also reviewed the effect of different LOD techniques.

Background

Women with PCOS have problems with ovulating and therefore may have difficulty becoming pregnant. In the past clomiphene citrate (CC) used to be the first-line treatment in women with PCOS. Ovulation induction with letrozole should be the first-line treatment according to new guidelines, but the use of letrozole is not officially approved. Consequently, clomiphene citrate is still commonly used. Approximately 20% of women on CC do not ovulate. When this occurs, we call it CC-resistant PCOS. For women with CC-resistant PCOS there are different medications available to induce ovulation, such as gonadotrophins, metformin or aromatase inhibitors, but these medications are not always successful and can cause adverse events like multiple pregnancies and cycle cancellation due to an excessive response. Another option for treatment is a surgical procedure called laparoscopic ovarian drilling (LOD). This involves applying heat or laser to the ovaries with a laparoscope (a camera) passed through a small cut, usually just below the belly button. This procedure is thought to improve the way the ovaries produce and respond to hormones, increasing the chance of ovulation. However, there are risks associated with surgery, such as complications from anaesthesia, infection, and adhesions. LOD is a surgical alternative to medical treatment, and this review aimed to determine its benefits and risks.

Study characteristics

In this updated review we included 38 controlled trials comparing LOD with medical ovulation induction or comparing different techniques of LOD. The evidence is current to October 2019

Key results

Our main analysis with low-quality evidence shows that LOD with and without medical ovulation induction may decrease the live birth rate slightly in women with anovulatory PCOS and CC-resistance compared with medical ovulation induction alone. Analysis including only the higher-quality RCTs shows uncertainty about any difference between the treatments. The evidence suggests that if the chance of live birth following medical ovulation induction alone is 44%, the chance following LOD would be between 32% and 52%. Moderate-quality evidence shows that LOD probably reduces the number of multiple pregnancies. The evidence suggests that if we assume the chance of a multiple pregnancy following medical ovulation induction alone to be 5.0%, the chance following LOD would be between 0.9% and 3.4%.

There may be little or no difference between the treatments for clinical pregnancy, and there is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage. Ovarian hyperstimulation syndrome (OHSS) may occur less often following LOD.

The quality of the evidence is not sufficient to justify a conclusion on live birth, clinical pregnancy or miscarriage for the analysis of unilateral LOD versus bilateral LOD.

The results of the primary outcomes for the other interventions were insufficient to enable us to draw any conclusions.

Quality of the evidence

The evidence was of very low to moderate quality. The main limitations in the evidence were poor reporting of study methods, the presence of bias introduced by the selection of individuals and variability in the results.

Authors' conclusions: 

Laparoscopic ovarian drilling with and without medical ovulation induction may decrease the live birth rate in women with anovulatory PCOS and CC resistance compared with medical ovulation induction alone. But the sensitivity analysis restricted to only RCTs at low risk of selection bias suggests there is uncertainty whether there is a difference between the treatments, due to uncertainty around the estimate. Moderate-quality evidence shows that LOD probably reduces the number of multiple pregnancy. Low-quality evidence suggests that there may be little or no difference between the treatments for the likelihood of a clinical pregnancy, and there is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage. LOD may result in less OHSS.

The quality of evidence is insufficient to justify a conclusion on live birth, clinical pregnancy or miscarriage rate for the analysis of unilateral LOD versus bilateral LOD. There were no data available on multiple pregnancy.

Read the full abstract...
Background: 

Polycystic ovary syndrome (PCOS) is a common condition affecting 8% to 13% of reproductive-aged women. In the past clomiphene citrate (CC) used to be the first-line treatment in women with PCOS. Ovulation induction with letrozole should be the first-line treatment according to new guidelines, but the use of letrozole is off-label. Consequently, CC is still commonly used. Approximately 20% of women on CC do not ovulate. Women who are CC-resistant can be treated with gonadotrophins or other medical ovulation-induction agents. These medications are not always successful, can be time-consuming and can cause adverse events like multiple pregnancies and cycle cancellation due to an excessive response. Laparoscopic ovarian drilling (LOD) is a surgical alternative to medical treatment. There are risks associated with surgery, such as complications from anaesthesia, infection, and adhesions.

Objectives: 

To evaluate the effectiveness and safety of LOD with or without medical ovulation induction compared with medical ovulation induction alone for women with anovulatory polycystic PCOS and CC-resistance.

Search strategy: 

We searched the Cochrane Gynaecology and Fertility Group (CGFG) trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trials registers up to 8 October 2019, together with reference checking and contact with study authors and experts in the field to identify additional studies.

Selection criteria: 

We included randomised controlled trials (RCTs) of women with anovulatory PCOS and CC resistance who underwent LOD with or without medical ovulation induction versus medical ovulation induction alone, LOD with assisted reproductive technologies (ART) versus ART, LOD with second-look laparoscopy versus expectant management, or different techniques of LOD.

Data collection and analysis: 

Two review authors independently selected studies, assessed risks of bias, extracted data and evaluated the quality of the evidence using the GRADE method. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS), ovulation, costs, and quality of life were secondary outcomes.

Main results: 

This updated review includes 38 trials (3326 women). The evidence was very low- to moderate-quality; the main limitations were due to poor reporting of study methods, with downgrading for risks of bias (randomisation and allocation concealment) and lack of blinding.

Laparoscopic ovarian drilling with or without medical ovulation induction versus medical ovulation induction alone

Pooled results suggest LOD may decrease live birth slightly when compared with medical ovulation induction alone (odds ratio (OR) 0.71, 95% confidence interval (CI) 0.54 to 0.92; 9 studies, 1015 women; I2 = 0%; low-quality evidence). The evidence suggest that if the chance of live birth following medical ovulation induction alone is 42%, the chance following LOD would be between 28% and 40%. The sensitivity analysis restricted to only RCTs with low risk of selection bias suggested there is uncertainty whether there is a difference between the treatments (OR 0.90, 95% CI 0.59 to 1.36; 4 studies, 415 women; I2 = 0%, low-quality evidence). LOD probably reduces multiple pregnancy rates (Peto OR 0.34, 95% CI 0.18 to 0.66; 14 studies, 1161 women; I2 = 2%; moderate-quality evidence). This suggests that if we assume the risk of multiple pregnancy following medical ovulation induction is 5.0%, the risk following LOD would be between 0.9% and 3.4%.

Restricting to RCTs that followed women for six months after LOD and six cycles of ovulation induction only, the results for live birth were consistent with the main analysis.

There may be little or no difference between the treatments for the likelihood of a clinical pregnancy (OR 0.86, 95% CI 0.72 to 1.03; 21 studies, 2016 women; I2 = 19%; low-quality evidence). There is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage (OR 1.11, 95% CI 0.78 to 1.59; 19 studies, 1909 women; I2 = 0%; low-quality evidence). OHSS was a very rare event. LOD may reduce OHSS (Peto OR 0.25, 95% CI 0.07 to 0.91; 8 studies, 722 women; I2 = 0%; low-quality evidence).

Unilateral LOD versus bilateral LOD

Due to the small sample size, the quality of evidence is insufficient to justify a conclusion on live birth (OR 0.83, 95% CI 0.24 to 2.78; 1 study, 44 women; very low-quality evidence).

There were no data available on multiple pregnancy.

The likelihood of a clinical pregnancy is uncertain between the treatments, due to the quality of the evidence and the large heterogeneity between the studies (OR 0.57, 95% CI 0.39 to 0.84; 7 studies, 470 women; I2 = 60%, very low-quality evidence). Due to the small sample size, the quality of evidence is not sufficient to justify a conclusion on miscarriage (OR 1.02, 95% CI 0.31 to 3.33; 2 studies, 131 women; I2 = 0%; very low-quality evidence).

Other comparisons

Due to lack of evidence and very low-quality data there is uncertainty whether there is a difference for any of the following comparisons: LOD with IVF versus IVF, LOD with second-look laparoscopy versus expectant management, monopolar versus bipolar LOD, and adjusted thermal dose versus fixed thermal dose.

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