The impact of laparoscopic ovarian drilling on AMH and ovarian reserve: a meta-analysis

in Reproduction
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  • 1 Department of Obstetrics and Gynaecology, University of Nottingham, Royal Derby Hospital, Derby, UK
  • 2 Derby Teaching Hospitals NHS Foundation Trust, Royal Derby Hospital, Derby, UK
  • 3 Department of Obstetrics and Gynaecology, The University of British Columbia, Vancouver, British Columbia, Canada

Correspondence should be addressed to S A Amer; Email: saad.amer@nottingham.ac.uk

(A H Yosef and A A Mohamed are now at Department of Obstetrics and Gynaecology, Assiut University, Assiut, Egypt)

Laparoscopic ovarian drilling (LOD) has been widely used as an effective treatment of anovulatory women with polycystic ovarian syndrome (PCOS). However, there has been a growing concern over a possible damaging effect of this procedure on ovarian reserve. The objective of this study was to investigate the hypothesis that LOD compromises ovarian reserve as measured by post-operative changes in circulating anti-Müllerian hormone (AMH). This meta-analysis included all cohort studies as well as randomised controlled trials (RCTs) investigating serum AMH concentrations and other ovarian reserve markers in women with PCOS undergoing LOD. Various databases were searched including MEDLINE, EMBASE, Dynamed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov and Cochrane Library from January 2000 to December 2016. Sixty studies were identified, of which seven were deemed eligible for this review. AMH data were extracted from each study and entered into the RevMan software to calculate the weighted mean difference (WMD) between pre- and post-operative values. Pooled analysis of all studies (n = 442) revealed a statistically significant decline in serum AMH concentration after LOD (WMD −2.13 ng/mL; 95% confidence interval (CI) −2.97 to −1.30). Subgroup analysis based on duration of follow-up, AMH kit, laterality of surgery and amount of energy applied during LOD consistently showed a statistically significant fall in serum AMH concentration. In conclusion, although LOD seems to markedly reduce circulating AMH, it remains uncertain whether this reflects a real damage to ovarian reserve or normalisation of the high pre-operative serum AMH levels. Further long-term studies on ovarian reserve after LOD are required to address this uncertainty.

Abstract

Laparoscopic ovarian drilling (LOD) has been widely used as an effective treatment of anovulatory women with polycystic ovarian syndrome (PCOS). However, there has been a growing concern over a possible damaging effect of this procedure on ovarian reserve. The objective of this study was to investigate the hypothesis that LOD compromises ovarian reserve as measured by post-operative changes in circulating anti-Müllerian hormone (AMH). This meta-analysis included all cohort studies as well as randomised controlled trials (RCTs) investigating serum AMH concentrations and other ovarian reserve markers in women with PCOS undergoing LOD. Various databases were searched including MEDLINE, EMBASE, Dynamed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov and Cochrane Library from January 2000 to December 2016. Sixty studies were identified, of which seven were deemed eligible for this review. AMH data were extracted from each study and entered into the RevMan software to calculate the weighted mean difference (WMD) between pre- and post-operative values. Pooled analysis of all studies (n = 442) revealed a statistically significant decline in serum AMH concentration after LOD (WMD −2.13 ng/mL; 95% confidence interval (CI) −2.97 to −1.30). Subgroup analysis based on duration of follow-up, AMH kit, laterality of surgery and amount of energy applied during LOD consistently showed a statistically significant fall in serum AMH concentration. In conclusion, although LOD seems to markedly reduce circulating AMH, it remains uncertain whether this reflects a real damage to ovarian reserve or normalisation of the high pre-operative serum AMH levels. Further long-term studies on ovarian reserve after LOD are required to address this uncertainty.

Introduction

Polycystic ovarian syndrome (PCOS) is a very common ovarian endocrinopathy with a prevalence of 6–20% among women of reproductive age (Yildiz et al. 2012) and about 90% among women with anovulatory of infertility (Hull 1987). It is characterised by a varied combination of clinical (anovulation and hyperandrogenism), biochemical (excess serum luteinizing hormone and androgen concentrations) and ovarian morphological (polycystic ovaries) features.

For anovulatory infertility in women with PCOS, laparoscopic ovarian drilling (LOD) has been well-established as a successful second-line treatment for ovulation induction after the failure of clomiphene citrate (Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2008, Farquhar et al. 2012). In addition to being as effective as gonadotrophin ovarian stimulation, LOD, offers several advantages over this treatment such as avoiding ovarian hyperstimulation syndrome and multiple pregnancies, reducing costs and negating the need for complex monitoring (Bayram et al. 2004, Farquhar et al. 2012). Furthermore, with LOD, a single treatment leads to repeated physiological ovulatory cycles and potentially repeated pregnancies without the need for repeated courses of medical treatment. Moreover, several follow-up studies provided evidence of long-term reproductive and endocrinological benefits of LOD (Gjønnæss 1998, Amer et al. 2002, Nahuis et al. 2012). We have previously reported long-term improvement in menstrual cycles and reproductive performance in about one-third of women with PCOS undergoing LOD for up to 9 years (Amer et al. 2002). Similarly, Nahuis and coworkers (Nahuis et al. 2012) followed women with PCOS for up to 12 years after LOD reporting high pregnancy rate (61% conception of a second child) with long-term improvement of menstrual cycles in 44% of cases.

Despite its proven efficacy, there has been a growing concern over the possible damaging effect of LOD on ovarian reserve. Our group and several other researchers have previously reported a significant reduction in serum anti-Müllerian hormone (AMH) after LOD (Weerakiet et al. 2007, Amer et al. 2009, Elmashad 2011, Farzadi et al. 2012, Sunj et al. 2014a, Syam et al. 2014, Giampaolino et al. 2016, Rezk et al. 2016). However, given the relatively small numbers of patients included in these studies, further evidence is required to allow a firm conclusion.

AMH is exclusively secreted by granulosa cells of growing follicles including primary, pre-antral, small antral (4–6 mm) and to less extent larger antral follicles (7–9 mm) (Weenen et al. 2004, Anderson et al. 2010). Thus, circulating AMH is now widely accepted as a reliable marker for ovarian reserve (Coccia & Rizzello 2008, Robertson 2008, Andersen et al. 2010). Furthermore, serum AMH concentration is generally stable with minimal inter- and intra-cycle fluctuations making it an ideal candidate for detecting small changes in ovarian reserve afterLOD (Lambert-Messerlian et al. 2016).

Based on the above, we have designed this systematic review and meta-analysis aiming to investigate the impact of LOD on ovarian reserve as determined mainly by serum AMH levels.

Materials and methods

This meta-analysis was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines (Liberati et al. 2009) and was registered in PROSPERO (CRD42016039687).

Inclusion criteria

This meta-analysis included all published cohort studies as well as randomised controlled trials (RCTs) that investigated changes in serum anti-Müllerian hormone (AMH) concentration in anovulatory women with PCOS undergoing LOD.

Outcome measures

Primary measure

This included post-operative changes in serum AMH concentration.

Secondary measures

These included post-operative changes in serum follicle stimulating hormone (FSH) concentration and antral follicle count (AFC) on ultrasound scan.

Search strategy

A detailed electronic search was conducted using numerous databases from January 2000 to June 2016 to identify studies investigating the effect of LOD on circulating AMH levels and other markers of ovarian reserve. Databases included MEDLINE (31 studies), Embase (29 studies), Dynamed (0), ScienceDirect (0), TRIP database (0), ClinicalTrials.gov (0) and the Cochrane Library (0). Medical Subject Headings (MeSH) terms used included: laparoscopy, PCOS, ovarian drilling, ovarian diathermy, ovarian electrocautery, ovarian reserve, AMH and antral follicle count. Search was limited to the English language, adult females of reproductive age. Three co-authors (A M, T E and A Y) conducted the searches and then an accredited clinical librarian (C J) independently repeated the search using the same criteria. All identified articles were retrieved, and their reference lists were manually checked for further relevant studies. Published conference abstracts, which could be identified from ScienceDirect database, were also considered for the analysis.

Study selection

Three investigators (A M, T E and A Y) independently screened the title and abstract of all identified articles to assess relevance to our meta-analysis. In case of disagreement, the full text was retrieved and reviewed independently by a senior author (S A) for a final decision.

All identified articles were evaluated according to a standardised format including study design, methods, participant characteristics, intervention and results. Three investigators scored the studies and collected the information independently (A M, T E, A Y). In case of discrepancies in scoring between the three investigators, a consensus was reached after discussion or after the involvement of the senior investigator (S A).

In two studies, the mean ± s.d. of serum AMH was missing as data were presented as median and range (Amer et al. 2009, Sunj et al. 2014a). The mean ± s.d. was also missing for AFC in two studies (Farzadi et al. 2012, Sunj et al. 2014a) and for FSH in four studies (Weerakiet et al. 2007, Sunj et al. 2014a, Giampaolino et al. 2016, Rezk et al. 2016). We obtained the mean ± s.d. of serum AMH and FSH levels from the original data of our previous study (Amer et al. 2009). Authors of other studies were contacted and three (Sunj et al. 2014a, Giampaolino et al. 2016, Rezk et al. 2016) responded providing the missing data.

Quality of included studies and risk of bias assessment

The modified Newcastle–Ottawa scale was used for assessing the quality and risk of bias of the included studies (Raffi et al. 2012, Mohamed et al. 2016). Each article was scored according to three categories including selection (maximum three stars), comparability (four stars) and outcomes (two stars). Selection was rated according to recruitment bias, selection of consecutive patients and power calculation. Comparability was assessed based on adjustment of analysis for four confounders including patients’ age (<40), baseline serum AMH, laterality of surgery and number of punctures according to estimated ovarian volume, type of instrument and energy used. Outcome was scored according to completeness of at least 3-month follow-up after surgery. In the current analysis, we have given more weight to comparability factors and used the cut-off level of six stars with a minimum of three stars in the comparability category (Raffi et al. 2012, Mohamed et al. 2016). Table 1 shows the results of quality scores of the studies included in this analysis.

Table 1

Modified Newcastle–Ottawa scale for risk of bias and quality assessment of the included studies.

Author and yearSelection (***)Comparability (****)Outcome (**)Overall
Amer et al. (2009)********8
Elmashad (2011)*******7
Farzadi et al. (2012)*******7
Seyam et al. (2014)********8
Sunj et al. (2014a)********8
Giampaolino et al. (2016)*******7
Rezk et al. (2016)********8

Data extraction and analysis

Pre- and post-operative mean ± s.d. serum AMH (ng/mL) and FSH (IU/mL) concentrations and AFC were extracted from the individual articles and were entered into the RevMan software (Review Manager, version 5.1, The Cochrane Collaboration, 2011; The Nordic Cochrane Centre, Copenhagen, Denmark) for meta-analysis. The weighted mean difference (WMD) between pre- and post-operative values was calculated. Statistical heterogeneity between studies was assessed by I-squared (I2) statistics and values of ≥50% were indicative of high heterogeneity (Higgins et al. 2003). When heterogeneity was significant, a random-effect model was used for meta-analysis. Fixed effect meta-analysis was used when there was no significant heterogeneity.

Overall analysis of data from all studies was first performed, irrespective of duration of the follow-up, laterality of surgery and type of AMH assay kit used. In studies with multiple measurements at different post-operative follow-up points, the latest AMH measurement was used for the overall analysis. In order to account for confounding factors, subgroup analyses were performed based on the duration of follow-up, AMH kits used, laterality (bilateral and unilateral) of LOD and amount of energy applied during LOD. No sensitivity analysis was performed as all the studies scored high on the modified Newcastle–Ottawa scale indicating low risk of bias (Table 1).

Results

The electronic database search identified 60 studies. All articles were screened and relevant articles were fully reviewed for eligibility for the study objectives and inclusion criteria. As a result, seven articles were deemed eligible for this meta-analysis (Fig. 1).

Figure 1
Figure 1

PRISMA flow chart of the study selection process.

Citation: Reproduction 154, 1; 10.1530/REP-17-0063

Excluded studies

Of the 60 identified articles, 51 did not use the AMH as a marker of ovarian reserve and were therefore excluded from this meta-analysis. Two further studies were excluded, one due to lack of pre-operative serum AMH levels (post-operative AMH levels were compared with a control group) (Weerakiet et al. 2007), and the other one (Sunj et al. 2014b) due to duplication of another study (Sunj et al. 2014a), which is included in the meta-analysis.

Included studies

Details of the seven studies are shown in Table 2.

Table 2

Characteristics of the seven studies included in the meta-analysis.

Authors and yearCountryDesignnAge (years) mean ± s.d.LateralityEnergy per ovary (J)FU (months)AMH assaySecondary outcomes
Amer et al. (2009)UKProspective cohort2928.4 ± 0.9Bilateral4506IOTFSH
Elmashad (2011)KuwaitProspective cohort2328.8 ± 3.1Bilateral4503IOTFSH, OV, AFC
Farzadi et al. (2012)IranProspective cohort3028.4 ± 2.3Bilateral***6EIAAFC
Seyam et al. (2014)EgyptProspective cohort4031.6 ± 4.5Bilateral480–9006IOTFSH, AFC
Sunj et al. (2014a)CroatiaProspective cohort9629.3 ± 3.3Unilateral: 496006Gen IIFSH, AFC, OV
29.3 ± 3.1Bilateral: 47~627
Giampaolino et al. (2016)ItalyRCT*11918–40**Bilateral480–12006DSLFSH
Rezk et al. (2016)EgyptRCT10529.7 ± 1.5Unilateral: 526006IOTAFC, FSH
29.8 ± 1.4Bilateral: 53~627

RCT Arm 1, laparoscopy included in the study; Arm 2, transvaginal hydrolaparoscopy excluded; **age range of participants, s.d. not available; ***6–7 punctures per ovary, but no data provided on energy; energy delivered as 60 J per 1 cm3 of ovarian volume, which is equivalent to 627 J per a 10 cm3 ovary.

DSL, diagnostic system laboratories; EIA, enzyme immunoassay (ELAab & USCNLIFE); ELISA, AMH kit; FU, follow up; J, Joules; IOT, immunotech AMH enzyme immunoassay; OV, ovarian volume; RCT, randomised controlled trial.

Study design

This systematic review included five cohort studies (Amer et al. 2009, Elmashad 2011, Farzadi et al. 2012, Seyam et al. 2014, Sunj et al. 2014a) and two RCTs (Giampaolino et al. 2016, Rezk et al. 2016). The RCT by Rezk and coworkers (Rezk et al. 2016) compared unilateral vs bilateral LOD. The two arms of this RCT were combined and used as a cohort study in the overall analysis, and then each arm was included separately in subgroup analysis. The other RCT compared laparoscopic vs transvaginal hydro-LOD (TH-LOD) (Giampaolino et al. 2016). Only the LOD group of this RCT was included as a cohort study in the current meta-analysis (Giampaolino et al. 2016).

Participants

All studies used appropriate selection criteria and all participants underwent the same surgical techniques of LOD. Inclusion and exclusion criteria were appropriately reported in all studies. All patients were accounted for all studies.

PCOS diagnosis

All seven studies included in this meta-analysis used the Rotterdam criteria for the diagnosis of PCOS (Amer et al. 2009, Elmashad 2011, Farzadi et al. 2012, Seyam et al. 2014, Sunj et al. 2014a, Giampaolino et al. 2016, Rezk et al. 2016).

Laparoscopic ovarian drilling

LOD was performed using monopolar diathermy needle in six studies (Amer et al. 2009, Elmashad 2011, Seyam et al. 2014, Sunj et al. 2014a, Giampaolino et al. 2016, Rezk et al. 2016). The remaining study used monopolar hook diathermy for LOD (Farzadi et al. 2012). One study randomised patients to undergo either LOD or TH-LOD, but only the LOD arm was included in the meta-analysis (Giampaolino et al. 2016).

With regard to the number of punctures and amount of energy delivered to the ovary during LOD, two studies reported four punctures per ovary at a power setting of 30 W applied for 5 s per puncture i.e. 450 joules (J) per ovary (Amer et al. 2009, Elmashad 2011). In the two studies comparing bilateral vs unilateral LOD, the authors applied 600 J per ovary (5 punctures × 4 s × 30 W) in the bilateral group and 60 J per 1 cm3 of ovarian volume in the unilateral group (delivered as 30 W for 4 s per puncture), which is equivalent to 627 J applied to a 10 cm3 ovary (Sunj et al. 2014a, Rezk et al. 2016). Seyam and coworkers reported 4–6 punctures per ovary at a power of 30 W for 4–5 s per puncture i.e. 480–900 J per ovary (Seyam et al. 2014). Giampaolino and coworkers (Giampaolino et al. 2016) applied 3–6 punctures per ovary using 40 W for 4–5 s per puncture i.e. 480–1200 J per ovary. One study reported 6–7 punctures per ovary, but no details were provided regarding the power setting or the duration of each puncture (Farzadi et al. 2012).

Concerning laterality, five studies reported that LOD was carried out bilaterally (Amer et al. 2009, Elmashad 2011, Farzadi et al. 2012, Seyam et al. 2014, Giampaolino et al. 2016). The remaining two studies compared unilateral vs bilateral LOD (Sunj et al. 2014a, Rezk et al. 2016).

Length of follow-up after LOD

Six studies completed 6-month follow-up after LOD, (Amer et al. 2009, Farzadi et al. 2012, Seyam et al. 2014, Sunj et al. 2014a, Giampaolino et al. 2016, Rezk et al. 2016) whereas the remaining study followed participants for 3 months (Elmashad 2011). Four studies carried out multiple measurements within 1 month (Amer et al. 2009, Farzadi et al. 2012, Seyam et al. 2014, Sunj et al. 2014a) and 3 months (Table 2) (Amer et al. 2009, Farzadi et al. 2012, Seyam et al. 2014, Rezk et al. 2016).

AMH kits

Four AMH kits were used in different studies (Table 2). Immunotech (IOT) AMH enzyme immunoassay kit (Immunotech, Beckman Coulter, Marseille, France) was used in four studies (Amer et al. 2009, Elmashad 2011, Seyam et al. 2014, Rezk et al. 2016). The intra- and inter-assay coefficients of variation for this AMH assay were below 12.3% and 14.2% respectively, with a detection limit of 0.14 ng/mL. The modified AMH Gen II enzyme-linked immunosorbent assay (ELISA) (Beckman Coulter, Chaska, MN, USA) was used by one study (Sunj et al. 2014a). The intra and inter-assay coefficients of variation for this AMH kit were both below 10%, with a detection limit of 0.08 ng/mL. Farzadi and coworkers (Farzadi et al. 2012) used AMH enzyme immunoassay (EIA) kit (ELAab & USCNLIFE, Wuhan ELAab Science Co. Ltd, Wuhan, China). The lowest detection limit of this assay is 0.053 ng/mL according to instructions provided in the analysis kit. The last study (Giampaolino et al. 2016) used DSL active AMH ELISA kit (Diagnostic Systems Laboratories, Webster, TX, USA). The intra- and inter-assay coefficients of variation for this kit were 4.6% and 8.0% respectively, with a detection limit of 0.017 ng/mL.

Antral follicle count

Four studies reported the AFC as an outcome measure of ovarian reserve (Elmashad 2011, Farzadi et al. 2012, Seyam et al. 2014, Rezk et al. 2016). The authors of another study provided the AFC data, which were missing from the published article, in response to our communication (Sunj et al. 2014a). Elmashad (2011) defined AFC as the number of follicles measuring 2–9 mm in diameter. Seyam and coworkers (Seyam et al. 2014) defined AFC as the count of all follicles measuring 2–10 mm in diameter. The remaining three studies did not define the size of the follicles used for the AFC, but reported using the Rotterdam definition of polycystic ovaries (>12 follicles measuring 2–9 mm) (Farzadi et al. 2012, Sunj et al. 2014a, Rezk et al. 2016).

Potential source of bias

In all seven studies, selection methods were clearly described and recruitment followed a consecutive manner. This made it possible to assess selection bias in all studies.

Overall pooled results

Table 3 shows mean ± s.d. serum AMH concentrations before and after LOD in all seven studies. Pooled analysis of all seven studies including 442 participants revealed a statistically significant decline of serum AMH concentration after LOD (WMD = −2.13 ng/mL; 95% confidence interval (CI) = −2.97 to −1.30). Heterogeneity between studies was high (I2 = 87%) (Fig. 2) (Amer et al. 2009, Elmashad 2011, Farzadi et al. 2012, Seyam et al. 2014, Sunj et al. 2014a, Giampaolino et al. 2016, Rezk et al. 2016).

Figure 2
Figure 2

WMD in serum AMH concentrations after laparoscopic ovarian drilling: pooled results for all seven studies. AMH, anti-Müllerian hormone; CI, confidence interval; WMD, weighted mean difference.

Citation: Reproduction 154, 1; 10.1530/REP-17-0063

Table 3

Pre- and post-operative serum AMH concentrations in all analysed studies.

Serum AMH (ng/mL), mean ± s.d.
ReferencenLateralityPre-operativePost-operative (1 month)Post-operative (3 months)Post-operative (6 months)
Amer et al. (2009)29Bilateral7.19 ± 5.06.75 ± 5.705.33 ± 3.903.68 ± 2.50
Elmashad (2011)23Bilateral7.40 ± 4.604.20 ± 2.50
Farzadi et al. (2012)30Bilateral8.40 ± 4.707.50 ± 4.507.00 ± 4.507.70 ± 4.40
Seyam et al. (2014)40Bilateral5.99 ± 2.303.40 ± 1.703.20 ± 1.703.10 ± 1.50
Sunj et al. (2014a)49Unilateral6.67 ± 2.895.02 ± 2.055.70 ± 2.05
47Bilateral7.42 ± 2.784.98 ± 1.685.60 ± 1.70
96Overall7.03 ± 2.855.00 ± 1.805.60 ± 1.80
Giampaolino et al. (2016)119Bilateral6.06 ± 1.185.00 ± 1.29
Rezk et al. (2016)52Unilateral8.60 ± 2.306.40 ± 1.206.50 ± 1.30
53Bilateral8.70 ± 2.405.20 ± 1.305.50 ± 1.10
105Overall8.60 ± 2.305.79 ± 1.305.90 ± 1.30

Subgroup analysis

Studies using different AMH assays

Pooled results of four studies (n = 197) using IOT AMH kit showed a statistically significant drop in serum AMH concentration (WMD, −2.80; 95% CI, −3.22 to −2.38; I2 = 0%) with low heterogeneity between studies (Amer et al. 2009, Elmashad 2011, Seyam et al. 2014, Rezk et al. 2016). Each of the other three AMH assays (Modified Gen II, DSL and Abbott Diagnostic kits) was used by one study and meta-analysis was therefore not possible (Farzadi et al. 2012, Sunj et al. 2014a, Giampaolino et al. 2016).

Studies with different length of follow-up

Analysis of four studies including 195 patients revealed a statistically significant decline in serum AMH concentration 1 month after LOD (WMD, −2.11; 95% CI, −2.62 to −1.59; I2 = 17%) (Amer et al. 2009, Farzadi et al. 2012, Seyam et al. 2014, Sunj et al. 2014a). Similarly, analysis of data from five studies (n = 277) with a 3-month follow-up showed a statistically significant fall in the serum AMH concentration after surgery (WMD, −2.74; 95% CI, −3.16 to −2.33; I2 = 0%) (Amer et al. 2009, Elmashad 2011, Farzadi et al. 2012, Seyam et al. 2014, Rezk et al. 2016). Analysis of six studies (n = 419) showed a statistically significant decline in the serum AMH concentration 6 months after LOD (WMD, −2.03; 95% CI −2.90 to −1.16; I2 = 88%) (Amer et al. 2009, Farzadi et al. 2012, Seyam et al. 2014, Sunj et al. 2014a, Giampaolino et al. 2016, Rezk et al. 2016).

Laterality of LOD

Bilateral LOD was performed in seven studies including 341 patients (Amer et al. 2009, Elmashad 2011, Farzadi et al. 2012, Seyam et al. 2014, Sunj et al. 2014a, Giampaolino et al. 2016, Rezk et al. 2016). Pooled analysis of these studies revealed a statistically significant drop in circulating serum AMH (WMD, −2.31; 95% CI, −3.29 to −1.33; I2 = 87%). Analysis of two studies (n = 101) measuring serum AMH changes after unilateral LOD showed a statistically significant decline in the post-operative serum AMH concentration (WMD, −1.59; 95% CI, −2.69 to −0.49; I2 = 69%) (Sunj et al. 2014a, Rezk et al. 2016).

Sub-analysis according to energy delivered to ovaries during LOD

Four studies including 253 patients used up to 600 J in ovarian drilling. Pooled analysis of these studies revealed a statistically significant drop in post-operative serum AMH levels (WMD, −2.45; 95% CI, −3.41 to −1.48; I2 = 72%) (Amer et al. 2009, Elmashad 2011, Sunj et al. 2014a, Rezk et al. 2016). Two studies with 159 patients were identified using up to 900–1200 J in ovarian drilling. Pooled analysis of the results showed a statistically significant decline in post-operative serum AMH concentrations (WMD, −1.93; 95% CI, −3.72 to −0.14; I2 = 94%) (Seyam et al. 2014, Giampaolino et al. 2016).

Secondary outcomes

Table 4 shows serum FSH concentrations before and after LOD in six studies (n = 412). Pooled analysis of these studies revealed no change in circulating FSH (WMD, 0.03; 95% CI, −0.46 to 0.52; I2 = 90%) (Amer et al. 2009, Elmashad 2011, Seyam et al. 2014, Sunj et al. 2014a, Giampaolino et al. 2016, Rezk et al. 2016).

Table 4

Pre- and post-operative serum FSH concentrations in all analysed studies.

Serum FSH (IU/L), mean ± s.d.
ReferencenLateralityPreoperativePostoperative (1 month)Postoperative (3 months)Postoperative (6 months)
Amer et al. (2009)29Bilateral5.3 ± 1.44.9±1.6
Elmashad (2011)23Bilateral4.9 ± 1.64.1 ± 1.4
Seyam et al. (2014)40Bilateral5.4 ± 2.75.7 ± 2.35.5 ± 2.15.45 ± 2.4
Sunj et al. (2014a)49Unilateral
47Bilateral
96Overall5.2 ± 1.175.7 ± 1.26.1 ± 1.2
Rezk et al. (2016)52Unilateral5.3 ± 1.45.41 ± 1.35.26 ± 1.4
53Bilateral5.5 ± 1.25.52 ± 1.35.49 ± 1.3
105Overall5.4 ± 1.35.3 ± 1.3

Five studies measured post-LOD changes in AFC, of which one was excluded due to lacking post-operative mean ± s.d. AFC (Farzadi et al. 2012). Table 5 shows AFC results of the included four studies. Pooled data of these studies showed no significant change in AFC (WMD, −3.46; 95% CI, −10.73 to 3.81; I2 = 99%) (Elmashad 2011, Seyam et al. 2014, Sunj et al. 2014a, Rezk et al. 2016). Further analysis was carried out to AFC follow-up within 3 and 6 months. Follow-up within 3 months were carried out with four studies including 264 patients. Pooled analysis of the results showed no significant changes in AFC after surgery (WMD, −5.51; 95% CI, −11.20 to 0.19; I2 = 99%) (Elmashad 2011, Seyam et al. 2014, Sunj et al. 2014a, Rezk et al. 2016). Three studies with 241 patients were identified performing follow-up assessment of AFC at 6 months. Pooled analysis of these studies revealed no significant changes to AFC after surgery (WMD, 0.04; 95% CI, −5.52 to 5.59; I2 = 98%) (Seyam et al. 2014, Sunj et al. 2014a, Rezk et al. 2016).

Table 5

Pre- and post-operative antral follicle count (AFC) in all analysed studies.

AFC, mean ± s.d.
ReferencenLateralityPre-operativePost-operative (1 month)Post-operative (3 months)Post-operative (6 months)
Elmashad (2011)23Bilateral29.0 ± 2.415.0 ± 2.2
Seyam et al. (2014)40Bilateral16.75 ± 3.214.2 ± 2.812.5 ± 2.612.2 ± 1.6
Sunj et al. (2014a)49Unilateral
47Bilateral
96Overall14.8 ± 2.714.8 ± 4.821.07 ± 8.2
Rezk et al. (2016)52Unilateral19.1 ± 5.415.2 ± 3.318.6 ± 3.1
53Bilateral18.9 ± 5.515.1 ± 3.216.4 ± 3.2
105Overall18.9 ± 5.415.1 ± 3.117.4 ± 3.3

Discussion

This is the first systematic review and meta-analysis to investigate the impact of LOD on ovarian reserve as determined by changes in post-operative serum AMH concentration. The overall analysis revealed a marked decline of 2.13 ng/mL, which represents 43% of the cut-off level of serum AMH concentration (4.9 ng/mL) in women with PCOS (Dewailly et al. 2011). This decline in circulating AMH seems to be sustained for up to 6 months after LOD. Further subgroup analysis taking into account all possible confounding factors consistently showed a significant decline in the post-operative serum AMH. The sub-analysis including studies with 1- and 3-month follow-up and studies using IOT AMH kit revealed low heterogeneity. This suggests that the high heterogeneity between studies seems to be due to variation in the follow-up periods and in the AMH assay kits used.

The exact mechanism of the post-LOD fall in circulating AMH remains uncertain. A possible explanation could be a decrease in AMH synthesis due to loss of the primary, pre-antral and small antral follicles, which are the main source of AMH, as a result of thermal damage during LOD (Weenen et al. 2004, Anderson et al. 2010). This hypothesis is further supported by the preliminary finding of an obvious trend towards a decline in AFC after LOD, although this did not reach statistical significance, possibly due to the small numbers involved in that analysis and high heterogeneity. Furthermore, we have recently reported a similar decline of circulating AMH after ovarian cystectomy (Raffi et al. 2012, Mohamed et al. 2016). This suggests that any surgical trauma to the ovary is associated with loss of ovarian follicles with subsequent reduction in AMH production. Whether this effect on AFC and AMH is temporary with subsequent recovery remains to be investigated with further long-term studies. Interestingly, two studies, which are included in this meta-analysis, reported a significant post-operative decline of AFC, which was sustained for up to 6 months in one study (Seyam et al. 2014), but seemed to have recovered at 6-month follow-up in the other study (Rezk et al. 2016). These conflicting data may explain the outcome of the pooled analysis, which revealed no significant change in AFC at 6-month follow-up. Further adequately designed short, medium and long-term cohort studies are required to address this issue.

It is interesting to see that even unilateral ovarian drilling caused a significant decline in circulating AMH, refuting the hypothesis that unilateral treatment could be less damaging to the ovarian reserve. It is worth mentioning that ovulation and pregnancy rates were higher in women undergoing bilateral vs unilateral ovarian drilling (Rezk et al. 2016). It is therefore possible to conclude that limiting the drilling to one ovary may compromise the success rates without any significant benefits to ovarian reserve. It was also interesting to see that despite the wide variation of the amount of energy used in different studies ranging between 450 and 1200 J per ovary, the decline in circulating AMH was more or less similar in all studies. This suggests that the range of energy doses used in these studies seem to be relatively safe to ovarian function with no excessive tissue damage with the higher doses.

One of the two RCTs in this meta-analysis compared AMH changes after LOD vs TH-LOD (Giampaolino et al. 2016). In order to minimise heterogeneity between studies, we decided to exclude the group undergoing TH-LOD due to the significant differences in techniques between this approach and the standard LOD used in all included studies. For example, TH-LOD uses bipolar diathermy, whilst LOD uses monopolar diathermy. Interestingly, there was no difference in the AMH changes after TH-LOD (pre-operative AMH, 5.84 ± 1.16 vs post-operative, 4.83 ± 1.10 ng/L, P < 0.0001) compared to LOD (6.06 ± 1.18 vs 5.00 ± 1.29 ng/L, P < 0.0001) (Giampaolino et al. 2016). This suggests that the degree of ovarian tissue damage is similar between the two energy modalities. This is surprising as bipolar diathermy is believed to reduce the risk of excessive ovarian tissue necrosis compared to monopolar energy.

It is well-known that serum AMH levels are generally stable with minimal inter- and intra-cycle variations and with a gradual decline (5.6% per year) with advancing age (Api 2009). We therefore believe that a 43% decline in AMH level after LOD is a marked drop. However, it is still uncertain whether this reflects a real decline in ovarian reserve or merely reflects normalisation of the high pre-operative serum AMH levels, which is a characteristic feature of PCOS (Amer et al. 2004). The well-established high pregnancy rates as well as the well-documented positive long-term reproductive effects of LOD favours the AMH normalisation hypothesis (Gjønnæss 1998, Amer et al. 2002, Api 2009). This is further supported by the lack of any effect of LOD on circulating FSH. However, further long-term studies of ovarian reserve after LOD are required to support one of the above two hypotheses. Based on our findings and until further long-term data become available, clinicians could continue to offer LOD to their patients with PCOS after carefully weighing the well-known benefits against the potential risks to ovarian reserve.

The main limitation of this review is the high heterogeneity between studies, possibly due to the variation in the AMH assay and amount of energy delivered to the ovary during LOD. Although, all studies used similar techniques of LOD, there were differences in the amount of energy delivered to the ovary with some studies applying 450–600 J per ovary (Amer et al. 2009, Elmashad 2011, Seyam et al. 2014, Rezk et al. 2016) whereas others delivering up to 900 J (Seyam et al. 2014) and 1200 J (Giampaolino et al. 2016) per ovary.

In conclusion, LOD significantly lowers the circulating AMH, but this may not necessarily reflect a real damage to the ovarian reserve. Given its proven efficacy and its long-term benefits, LOD should remain as an option in the management of anovulatory inpatients with PCOS.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding

This work was supported by the Egyptian Cultural Centre and Education bureau in London and the British Council in Cairo.

Acknowledgements

The authors are grateful to the funders including the Egyptian Cultural Centre and Education bureau in London and the British Council in Cairo for supporting this work.

References

  • Amer SA, Gopalan V, Li TC, Ledger WL & Cooke ID 2002 Long term follow-up of patients with polycystic ovarian syndrome after laparoscopic ovarian drilling: clinical outcome. Human Reproduction 17 20352042. (doi:10.1093/humrep/17.8.2035)

    • Search Google Scholar
    • Export Citation
  • Amer SA, Li TC & Ledger WL 2004 Ovulation induction using laparoscopic ovarian drilling in women with polycystic ovarian syndrome: predictors of success. Human Reproduction 19 17191724. (doi:10.1093/humrep/deh343)

    • Search Google Scholar
    • Export Citation
  • Amer SA, Li TC & Ledger WL 2009 The value of measuring anti-Müllerian hormone in women with anovulatory polycystic ovary syndrome undergoing laparoscopic ovarian diathermy. Human Reproduction 24 27602766. (doi:10.1093/humrep/dep271)

    • Search Google Scholar
    • Export Citation
  • Api M 2009 Is ovarian reserve diminished after laparoscopic ovarian drilling? Gynecological Endocrinolology 25 159165. (doi:10.1080/09513590802585605)

    • Search Google Scholar
    • Export Citation
  • Andersen CY, Schmidt KT, Kristensen SG, Rosendahl M, Byskov AG & Ernst E 2010 Concentrations of AMH and inhibin-B in relation to follicular diameter in normal human small antral follicles. Human Reproduction 25 12821287. (doi:10.1093/humrep/deq019)

    • Search Google Scholar
    • Export Citation
  • Bayram N, Van Wely M, Kaaijk EM, Bossuyt PM & van der Veen F 2004 Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial. British Medical Journal 328 192. (doi:10.1136/bmj.328.7433.192)

    • Search Google Scholar
    • Export Citation
  • Coccia ME & Rizzello F 2008 Ovarian reserve. Annals of the New York Academy of Sciences 1127 2730. (doi:10.1196/annals.1434.011)

  • Dewailly D, Gronier H, Poncelet E, Robin G, Leroy M, Pigny P, Duhamel A & Catteau-Jonard S 2011 Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries. Human Reproduction 26 31233129. (doi:10.1093/humrep/der297)

    • Search Google Scholar
    • Export Citation
  • Elmashad AI 2011 Impact of laparoscopic ovarian drilling on anti-Müllerian hormone levels and ovarian stromal blood flow using three-dimensional power Doppler in women with anovulatory polycystic ovary syndrome. Fertility and Sterility 95 23422346. (doi:10.1016/j.fertnstert.2011.03.093)

    • Search Google Scholar
    • Export Citation
  • Farquhar C, Brown J & Marjoribanks J 2012 Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Library 13 CD001122. (doi:10.1002/14651858.CD001122.pub4)

    • Search Google Scholar
    • Export Citation
  • Farzadi L, Nouri M, Ghojazadeh M, Mohiti M & Aghadavod E 2012 Evaluation of ovarian reserve after laparoscopic surgery in patients with polycystic ovary syndrome. Bioimpacts 2 167170. (doi:10.5681/bi.2012.018)

    • Search Google Scholar
    • Export Citation
  • Giampaolino P, Morra I, Della Corte L, Sparice S, Di Carlo C, Nappi C & Bifulco G 2016 Serum anti-Mullerian hormone levels after ovarian drilling for the second-line treatment of polycystic ovary syndrome: a pilot-randomized study comparing laparoscopy and transvaginal hydrolaparoscopy. Gynecololical Endocrinology 24 14. (doi:10.1080/09513590.2016.1188280)

    • Search Google Scholar
    • Export Citation
  • Gjønnæss H 1998 Late endocrine effects of ovarian electrocautery in women with polycystic ovary syndrome. Fertility and Sterility 69 697701. (doi:10.1016/S0015-0282(98)00006-5)

    • Search Google Scholar
    • Export Citation
  • Higgins JP, Thompson SG, Deeks JJ & Altman DG 2003 Measuring inconsistency in meta-analyses. British Medical Journal 327 557560. (doi:10.1136/bmj.327.7414.557)

    • Search Google Scholar
    • Export Citation
  • Hull MG 1987 Epidemiology of infertility and polycystic ovarian disease: endocrinological and demographic studies. Gynecololical Endocrinology 1 235245. (doi:10.3109/09513598709023610)

    • Search Google Scholar
    • Export Citation
  • Lambert-Messerlian G, Plante B, Eklund EE, Raker C & Moore RG 2016 Levels of antimüllerian hormone in serum during the normal menstrual cycle. Fertility and Sterility 105 208213. (doi:10.1016/j.fertnstert.2015.09.033)

    • Search Google Scholar
    • Export Citation
  • Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J & Moher D 2009 The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Annals of Internal Medicine 151 W65W94. (doi:10.1136/bmj.b2700)

    • Search Google Scholar
    • Export Citation
  • Mohamed AA, Al-Hussaini TK, Fathalla MM, El Shamy TT, Abdelaal II & Amer SA 2016 The impact of excision of benign non-endometriotic ovarian cysts on ovarian reserve: a systematic review. American Journal Obstetrics and Gynecolology 215 169176. (doi:10.1016/j.ajog.2016.03.045)

    • Search Google Scholar
    • Export Citation
  • Nahuis MJ, Oude Lohuis E, Kose N, Bayram N, Hompes P, Oosterhuis GJ, Kaaijk EM, Cohlen BJ, Bossuyt PP & van der Veen F 2012 Long-term follow-up of laparoscopic electrocautery of the ovaries versus ovulation induction with recombinant FSH in clomiphene citrate-resistant women with polycystic ovary syndrome: an economic evaluation. Human Reproduction 27 35773582. (doi:10.1093/humrep/des336)

    • Search Google Scholar
    • Export Citation
  • Raffi F, Metwally M & Amer S 2012 The impact of excision of ovarian endometrioma on ovarian reserve: a systematic review and meta-analysis. Journal of Clinical Endocrinolology and Metabolism 97 31463154. (doi:10.1210/jc.2012-1558)

    • Search Google Scholar
    • Export Citation
  • Rezk M, Sayyed T & Saleh S 2016 Impact of unilateral versus bilateral laparoscopic ovarian drilling on ovarian reserve and pregnancy rate: a randomized clinical trial. Gynecological Endocrinology 32 399402. (doi:10.3109/09513590.2015.1124262)

    • Search Google Scholar
    • Export Citation
  • Robertson DM 2008 Anti-Müllerian hormone as a marker of ovarian reserve: an update. Womens Health 4 137141. (doi:10.2217/17455057.4.2.137)

    • Search Google Scholar
    • Export Citation
  • Seyam EM, Mohamed TG, Hasan MM & Al Mawgood MH 2014 Evaluation of ultrasonographic and Anti-Müllerian Hormone (AMH) changes as predictors for ovarian reserve after laparoscopic ovarian drilling for women with polycystic ovarian syndrome. Middle East Fertility Society Journal 19 314323. (doi:10.1016/j.mefs.2014.02.004)

    • Search Google Scholar
    • Export Citation
  • Sunj M, Canic T, Jeroncic A, Karelovic D, Tandara M, Juric S & Palada I 2014a Anti-Müllerian hormone, testosterone and free androgen index following the dose-adjusted unilateral diathermy in women with polycystic ovary syndrome. European Journal Obstetetrics Gynecology and Reproductive Biology 179 163169. (doi:10.1016/j.ejogrb.2014.05.011)

    • Search Google Scholar
    • Export Citation
  • Sunj M, Kasum M, Canic T, Karelovic D, Tandara M, Tandara L & Palada I 2014b Assessment of ovarian reserve after unilateral diathermy with thermal doses adjusted to ovarian volume. Gynecololical Endocrinology 30 785788. (doi:10.3109/09513590.2014.929656)

    • Search Google Scholar
    • Export Citation
  • Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2008 Consensus on infertility treatment related to polycystic ovary syndrome. Fertility and Sterility 89 505522. (doi:10.1016/j.fertnstert.2007.09.041)

    • Search Google Scholar
    • Export Citation
  • Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, Kramer P, Fauser BC & Themmen AP 2004 Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mollecular Human Reproduction 10 7783. (doi:10.1093/molehr/gah015)

    • Search Google Scholar
    • Export Citation
  • Weerakiet S, Lertvikool S, Tingthanatikul Y, Wansumrith S, Leelaphiwat S & Jultanmas R 2007 Ovarian reserve in women with polycystic ovary syndrome who underwent laparoscopic ovarian drilling. Gynecological Endocrinology 23 455460. (doi:10.1080/09513590701485212)

    • Search Google Scholar
    • Export Citation
  • Yildiz BO, Bozdag G, Yapici Z, Esinler I & Yarali H 2012 Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Human Reproduction 27 30673073. (doi:10.1093/humrep/des232)

    • Search Google Scholar
    • Export Citation

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    PRISMA flow chart of the study selection process.

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    WMD in serum AMH concentrations after laparoscopic ovarian drilling: pooled results for all seven studies. AMH, anti-Müllerian hormone; CI, confidence interval; WMD, weighted mean difference.

  • Amer SA, Gopalan V, Li TC, Ledger WL & Cooke ID 2002 Long term follow-up of patients with polycystic ovarian syndrome after laparoscopic ovarian drilling: clinical outcome. Human Reproduction 17 20352042. (doi:10.1093/humrep/17.8.2035)

    • Search Google Scholar
    • Export Citation
  • Amer SA, Li TC & Ledger WL 2004 Ovulation induction using laparoscopic ovarian drilling in women with polycystic ovarian syndrome: predictors of success. Human Reproduction 19 17191724. (doi:10.1093/humrep/deh343)

    • Search Google Scholar
    • Export Citation
  • Amer SA, Li TC & Ledger WL 2009 The value of measuring anti-Müllerian hormone in women with anovulatory polycystic ovary syndrome undergoing laparoscopic ovarian diathermy. Human Reproduction 24 27602766. (doi:10.1093/humrep/dep271)

    • Search Google Scholar
    • Export Citation
  • Api M 2009 Is ovarian reserve diminished after laparoscopic ovarian drilling? Gynecological Endocrinolology 25 159165. (doi:10.1080/09513590802585605)

    • Search Google Scholar
    • Export Citation
  • Andersen CY, Schmidt KT, Kristensen SG, Rosendahl M, Byskov AG & Ernst E 2010 Concentrations of AMH and inhibin-B in relation to follicular diameter in normal human small antral follicles. Human Reproduction 25 12821287. (doi:10.1093/humrep/deq019)

    • Search Google Scholar
    • Export Citation
  • Bayram N, Van Wely M, Kaaijk EM, Bossuyt PM & van der Veen F 2004 Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial. British Medical Journal 328 192. (doi:10.1136/bmj.328.7433.192)

    • Search Google Scholar
    • Export Citation
  • Coccia ME & Rizzello F 2008 Ovarian reserve. Annals of the New York Academy of Sciences 1127 2730. (doi:10.1196/annals.1434.011)

  • Dewailly D, Gronier H, Poncelet E, Robin G, Leroy M, Pigny P, Duhamel A & Catteau-Jonard S 2011 Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries. Human Reproduction 26 31233129. (doi:10.1093/humrep/der297)

    • Search Google Scholar
    • Export Citation
  • Elmashad AI 2011 Impact of laparoscopic ovarian drilling on anti-Müllerian hormone levels and ovarian stromal blood flow using three-dimensional power Doppler in women with anovulatory polycystic ovary syndrome. Fertility and Sterility 95 23422346. (doi:10.1016/j.fertnstert.2011.03.093)

    • Search Google Scholar
    • Export Citation
  • Farquhar C, Brown J & Marjoribanks J 2012 Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Library 13 CD001122. (doi:10.1002/14651858.CD001122.pub4)

    • Search Google Scholar
    • Export Citation
  • Farzadi L, Nouri M, Ghojazadeh M, Mohiti M & Aghadavod E 2012 Evaluation of ovarian reserve after laparoscopic surgery in patients with polycystic ovary syndrome. Bioimpacts 2 167170. (doi:10.5681/bi.2012.018)

    • Search Google Scholar
    • Export Citation
  • Giampaolino P, Morra I, Della Corte L, Sparice S, Di Carlo C, Nappi C & Bifulco G 2016 Serum anti-Mullerian hormone levels after ovarian drilling for the second-line treatment of polycystic ovary syndrome: a pilot-randomized study comparing laparoscopy and transvaginal hydrolaparoscopy. Gynecololical Endocrinology 24 14. (doi:10.1080/09513590.2016.1188280)

    • Search Google Scholar
    • Export Citation
  • Gjønnæss H 1998 Late endocrine effects of ovarian electrocautery in women with polycystic ovary syndrome. Fertility and Sterility 69 697701. (doi:10.1016/S0015-0282(98)00006-5)

    • Search Google Scholar
    • Export Citation
  • Higgins JP, Thompson SG, Deeks JJ & Altman DG 2003 Measuring inconsistency in meta-analyses. British Medical Journal 327 557560. (doi:10.1136/bmj.327.7414.557)

    • Search Google Scholar
    • Export Citation
  • Hull MG 1987 Epidemiology of infertility and polycystic ovarian disease: endocrinological and demographic studies. Gynecololical Endocrinology 1 235245. (doi:10.3109/09513598709023610)

    • Search Google Scholar
    • Export Citation
  • Lambert-Messerlian G, Plante B, Eklund EE, Raker C & Moore RG 2016 Levels of antimüllerian hormone in serum during the normal menstrual cycle. Fertility and Sterility 105 208213. (doi:10.1016/j.fertnstert.2015.09.033)

    • Search Google Scholar
    • Export Citation
  • Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J & Moher D 2009 The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Annals of Internal Medicine 151 W65W94. (doi:10.1136/bmj.b2700)

    • Search Google Scholar
    • Export Citation
  • Mohamed AA, Al-Hussaini TK, Fathalla MM, El Shamy TT, Abdelaal II & Amer SA 2016 The impact of excision of benign non-endometriotic ovarian cysts on ovarian reserve: a systematic review. American Journal Obstetrics and Gynecolology 215 169176. (doi:10.1016/j.ajog.2016.03.045)

    • Search Google Scholar
    • Export Citation
  • Nahuis MJ, Oude Lohuis E, Kose N, Bayram N, Hompes P, Oosterhuis GJ, Kaaijk EM, Cohlen BJ, Bossuyt PP & van der Veen F 2012 Long-term follow-up of laparoscopic electrocautery of the ovaries versus ovulation induction with recombinant FSH in clomiphene citrate-resistant women with polycystic ovary syndrome: an economic evaluation. Human Reproduction 27 35773582. (doi:10.1093/humrep/des336)

    • Search Google Scholar
    • Export Citation
  • Raffi F, Metwally M & Amer S 2012 The impact of excision of ovarian endometrioma on ovarian reserve: a systematic review and meta-analysis. Journal of Clinical Endocrinolology and Metabolism 97 31463154. (doi:10.1210/jc.2012-1558)

    • Search Google Scholar
    • Export Citation
  • Rezk M, Sayyed T & Saleh S 2016 Impact of unilateral versus bilateral laparoscopic ovarian drilling on ovarian reserve and pregnancy rate: a randomized clinical trial. Gynecological Endocrinology 32 399402. (doi:10.3109/09513590.2015.1124262)

    • Search Google Scholar
    • Export Citation
  • Robertson DM 2008 Anti-Müllerian hormone as a marker of ovarian reserve: an update. Womens Health 4 137141. (doi:10.2217/17455057.4.2.137)

    • Search Google Scholar
    • Export Citation
  • Seyam EM, Mohamed TG, Hasan MM & Al Mawgood MH 2014 Evaluation of ultrasonographic and Anti-Müllerian Hormone (AMH) changes as predictors for ovarian reserve after laparoscopic ovarian drilling for women with polycystic ovarian syndrome. Middle East Fertility Society Journal 19 314323. (doi:10.1016/j.mefs.2014.02.004)

    • Search Google Scholar
    • Export Citation
  • Sunj M, Canic T, Jeroncic A, Karelovic D, Tandara M, Juric S & Palada I 2014a Anti-Müllerian hormone, testosterone and free androgen index following the dose-adjusted unilateral diathermy in women with polycystic ovary syndrome. European Journal Obstetetrics Gynecology and Reproductive Biology 179 163169. (doi:10.1016/j.ejogrb.2014.05.011)

    • Search Google Scholar
    • Export Citation
  • Sunj M, Kasum M, Canic T, Karelovic D, Tandara M, Tandara L & Palada I 2014b Assessment of ovarian reserve after unilateral diathermy with thermal doses adjusted to ovarian volume. Gynecololical Endocrinology 30 785788. (doi:10.3109/09513590.2014.929656)

    • Search Google Scholar
    • Export Citation
  • Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2008 Consensus on infertility treatment related to polycystic ovary syndrome. Fertility and Sterility 89 505522. (doi:10.1016/j.fertnstert.2007.09.041)

    • Search Google Scholar
    • Export Citation
  • Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, Kramer P, Fauser BC & Themmen AP 2004 Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mollecular Human Reproduction 10 7783. (doi:10.1093/molehr/gah015)

    • Search Google Scholar
    • Export Citation
  • Weerakiet S, Lertvikool S, Tingthanatikul Y, Wansumrith S, Leelaphiwat S & Jultanmas R 2007 Ovarian reserve in women with polycystic ovary syndrome who underwent laparoscopic ovarian drilling. Gynecological Endocrinology 23 455460. (doi:10.1080/09513590701485212)

    • Search Google Scholar
    • Export Citation
  • Yildiz BO, Bozdag G, Yapici Z, Esinler I & Yarali H 2012 Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Human Reproduction 27 30673073. (doi:10.1093/humrep/des232)

    • Search Google Scholar
    • Export Citation