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 METHODS: 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.
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.
BACKGROUND: Adhesions are fibrin bands that are a common consequence of gynaecological surgery. They are caused by conditions that include pelvic inflammatory disease and endometriosis. Adhesions are associated with comorbidities, including pelvic pain, subfertility, and small bowel obstruction. Adhesions also increase the likelihood of further surgery, causing distress and unnecessary expenses. Strategies to prevent adhesion formation include the use of fluid (also called hydroflotation) and gel agents, which aim to prevent healing tissues from touching one another, or drugs, aimed to change an aspect of the healing process, to make adhesions less likely to form.
OBJECTIVES: To evaluate the effectiveness and safety of fluid and pharmacological agents on rates of pain, live births, and adhesion prevention in women undergoing gynaecological surgery.
SEARCH METHODS: We searched: the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and Epistemonikos to 22 August 2019. We also checked the reference lists of relevant papers and contacted experts in the field.
SELECTION CRITERIA: Randomised controlled trials investigating the use of fluid (including gel) and pharmacological agents to prevent adhesions after gynaecological surgery.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. We assessed the overall quality of the evidence using GRADE methods. Outcomes of interest were pelvic pain; live birth rates; incidence of, mean, and changes in adhesion scores at second look-laparoscopy (SLL); clinical pregnancy, miscarriage, and ectopic pregnancy rates; quality of life at SLL; and adverse events.
MAIN RESULTS: We included 32 trials (3492 women), and excluded 11. We were unable to include data from nine studies in the statistical analyses, but the findings of these studies were broadly in keeping with the findings of the meta-analyses. Hydroflotation agents versus no hydroflotation agents (10 RCTs) We are uncertain whether hydroflotation agents affected pelvic pain (odds ratio (OR) 1.05, 95% confidence interval (CI) 0.52 to 2.09; one study, 226 women; very low-quality evidence). It is unclear whether hydroflotation agents affected live birth rates (OR 0.67, 95% CI 0.29 to 1.58; two studies, 208 women; low-quality evidence) compared with no treatment. Hydroflotation agents reduced the incidence of adhesions at SLL when compared with no treatment (OR 0.34, 95% CI 0.22 to 0.55, four studies, 566 women; high-quality evidence). The evidence suggests that in women with an 84% chance of having adhesions at SLL with no treatment, using hydroflotation agents would result in 54% to 75% having adhesions. Hydroflotation agents probably made little or no difference to mean adhesion score at SLL (standardised mean difference (SMD) -0.06, 95% CI -0.20 to 0.09; four studies, 722 women; moderate-quality evidence). It is unclear whether hydroflotation agents affected clinical pregnancy rate (OR 0.64, 95% CI 0.36 to 1.14; three studies, 310 women; moderate-quality evidence) compared with no treatment. This suggests that in women with a 26% chance of clinical pregnancy with no treatment, using hydroflotation agents would result in a clinical pregnancy rate of 11% to 28%. No studies reported any adverse events attributable to the intervention. Gel agents versus no treatment (12 RCTs) No studies in this comparison reported pelvic pain or live birth rate. Gel agents reduced the incidence of adhesions at SLL compared with no treatment (OR 0.26, 95% CI 0.12 to 0.57; five studies, 147 women; high-quality evidence). This suggests that in women with an 84% chance of having adhesions at SLL with no treatment, the use of gel agents would result in 39% to 75% having adhesions. It is unclear whether gel agents affected mean adhesion scores at SLL (SMD -0.50, 95% CI -1.09 to 0.09; four studies, 159 women; moderate-quality evidence), or clinical pregnancy rate (OR 0.20, 95% CI 0.02 to 2.02; one study, 30 women; low-quality evidence). No studies in this comparison reported on adverse events attributable to the intervention. Gel agents versus hydroflotation agents when used as an instillant (3 RCTs) No studies in this comparison reported pelvic pain, live birth rate or clinical pregnancy rate. Gel agents probably reduce the incidence of adhesions at SLL when compared with hydroflotation agents (OR 0.50, 95% CI 0.31 to 0.83; three studies, 538 women; moderate-quality evidence). This suggests that in women with a 46% chance of having adhesions at SLL with a hydroflotation agent, the use of gel agents would result in 21% to 41% having adhesions. We are uncertain whether gel agents improved mean adhesion scores at SLL when compared with hydroflotation agents (MD -0.79, 95% CI -0.82 to -0.76; one study, 77 women; very low-quality evidence). No studies in this comparison reported on adverse events attributable to the intervention. Steroids (any route) versus no steroids (4 RCTs) No studies in this comparison reported pelvic pain, incidence of adhesions at SLL or mean adhesion score at SLL. It is unclear whether steroids affected live birth rates compared with no steroids (OR 0.65, 95% CI 0.26 to 1.62; two studies, 223 women; low-quality evidence), or clinical pregnancy rates (OR 1.01, 95% CI 0.66 to 1.55; three studies, 410 women; low-quality evidence). No studies in this comparison reported on adverse events attributable to the intervention.
AUTHORS' CONCLUSIONS: Gels and hydroflotation agents appear to be effective adhesion prevention agents for use during gynaecological surgery, but we found no evidence indicating that they improve fertility outcomes or pelvic pain, and further research is required in this area. It is also worth noting that for some comparisons, wide confidence intervals crossing the line of no effect meant that clinical harm as a result of interventions could not be excluded. Future studies should measure outcomes in a uniform manner, using the modified American Fertility Society score. Statistical findings should be reported in full. No studies reported any adverse events attributable to intervention.
CONTESTO: Dopo l'introduzione di fecondazione in vitro (IVF) chirurgia tubarica è stata meno frequente come una tecnica per migliorare la fertilità nelle donne con danni alle tube di Falloppio. Esistono varie tecniche chirurgiche che possono essere utilizzate per riparare bloccati o danneggiati tube di Falloppio.
OBIETTIVI: Per valutare il ruolo della chirurgia tubarica nella gestione di infertilità tubarica e valutare tecniche chirurgiche per il trattamento della infertilità tubarica.
Metodi di ricerca: Questa recensione è disegnato sulla strategia di ricerca sviluppato per i disturbi mestruali e del Gruppo Subfertility. Sono stati identificati studi rilevanti dal Cochrane Disturbi mestruali e Subfertility Gruppo specializzato Registri (cercato fino a luglio 2005) e Cochrane Central Register of Controlled Trials (CENTRAL). Le basi di dati seguenti sono stati perquisiti utilizzando la piattaforma OVID:
1. MEDLINE (dal 1966 a luglio 2005);
2. EMBASE (dal 1980 a luglio 2005).
CRITERI DI SELEZIONE: Tutti gli studi randomizzati e controllati che indagano i seguenti argomenti di tecnica infertilità chirurgia come segue sono stati inclusi.
1) Il ruolo della chirurgia dell'infertilità contro nessun trattamento.
2) Il ruolo della chirurgia contro l'infertilità trattamenti alternativi.
3) Il ruolo di ingrandimento.
4) Il ruolo del laser CO2 in chirurgia infertilità.
5) Il ruolo della laparoscopia operativa per eseguire un intervento chirurgico infertilità.
6) Qualsiasi altro intervento per quanto riguarda la tecnica chirurgica di indagine da RCT.
Raccolta dati e analisi: I dati sono stati estratti indipendentemente dai primi due autori. Le differenze di opinione sono stati riconosciuti e risolti per consenso.
Due a due tavoli sono stati generati per ogni prova per l'esito dicotomico di gravidanza e gli effetti sul tasso di gravidanza di ciascuno studio è espresso come odds ratio con intervalli di confidenza al 95%.
Risultati principali: sette studi randomizzati e controllati sono stati identificati. Non ci sono studi randomizzati di confronto chirurgia dell'infertilità contro nessun trattamento o in alternativa di trattamento sono stati trovati. Non c'era studio ha trovato che indaga sull'uso di ingrandimento per la chirurgia tubarica.
Non c'è evidenza a favore o contro l'uso di un laser CO2 rispetto alle tecniche standard per adesiolisi (OR per la gravidanza 1.07, 95% CI 0,40-2,87) o salpingostomy (OR per la gravidanza 1,38, 95% CI 0,47-4,05) da due RCT .
Un RCT donne randomizzate per salpingostomatolysis da laparotomia e laparoscopia utilizzando il metodo classico o quella tecnica di sutura. Non c'è evidenza di beneficio o svantaggio quando laparoscopia è stato confrontato con laparotomia. L'OR per la pervietà tubarica bilaterale era 1.32 (95% CI 0,55-3,22) e unilaterale pervietà tubarica OR era 0,82 (IC 95% 0,29-2,29). Il tasso di gravidanza non è stata riportata.
Non c'è evidenza di beneficio o svantaggio di due studi randomizzati per valutare l'uso di una protesi al salpingostomy rispetto con quote combinate di non-uso (di gravidanza (termine) in gruppo utilizzando la protesi rispetto al controllo (OR per gravidanza a termine 1,17, 95% CI 0,47-2,93).
Non c'è stata evidenza di differenza vantaggio o svantaggio in un manicotto RCT confronto contro tecnica Bruhat per salpingostomy Un RCT ha confrontato due metodi di salpingostomy (OR per il tasso di gravidanza (intrauterina) 1.02, 95% CI 0,22-4,61).
Un RCT ha mostrato alcuna evidenza di beneficio o svantaggio per l'uso di termocoagulazione o elettrocoagulazione al adesiolisi, quote per il tasso di gravidanza tra i due gruppi OR 0,87 (IC 95% 0,51-1,46).
Conclusioni degli autori: Da questi dati limitati non vi è alcuna evidenza di un beneficio o svantaggio di chirurgia tubarica versus nessun trattamento o trattamenti alternativi. Allo stesso modo non vi è alcuna prova di un vantaggio o svantaggio di usare microchirurgia rispetto alle tecniche standard; approccio laparoscopico nel laparotomia, l'uso di laser a CO2, o elettrocoagulazione su termocoagulazione.
Trials randomizzati e controllati dovrebbero essere intraprese per determinare il ruolo della chirurgia tubarica versus nessun trattamento o trattamenti alternativi.
Trials randomizzati e controllati dovrebbero essere intraprese per determinare il ruolo di chirurgia tubarica di ingrandimento, l'approccio laparoscopico, l'uso di laser o elettrocoagulazione.
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 METHODS:
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.
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.
