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Do women with endometrioma and/or DIE have poorer IVF/ICSI outcomes when compared to those without disease?
Does surgery prior to ART affect IVF/ICSI outcomes in women with endometrioma and/or DIE?
Does variation of surgical techniques influence IVF/ICSI outcomes?
Review questions
Systematic reviews and meta-analyses by Benschop et al (2010) and Tsoumpo et al (2009) have both found no evidence of benefit on IVF/ICSI outcomes when comparing surgery for endometrioma prior to ART and expectant management. There is limited data on the impact of surgery for DIE prior to ART. In a review based on uncontrolled studies by Vercellini et al in 2009, concluded benefits from surgery appear smaller than previously thought and the authors emphasisedthe need for further clarification
The presence of endometriosis is known to be detrimental to fertility. Many patients with endometrioma and/or DIE may eventually require ART to achieve a pregnancy. Strategies on improving the reproductive outcome in women with endometrioma and/or DIE are limited to the use of GnRH agonist down regulation prior to the ART cycles (Sallam et al) or surgery. Recent ESHRE guidance has not been able to provide definitive guidance (ESHRE 2013). Nevertheless, surgical treatment prior to ART is widely practiced
Introduction
Previous reviews
n=913
Records identified through initial database screening
n=645
Full-text articles assessed for eligibility
n=68
Studies included in data synthesis
n=33
Final studies included in meta-analysis
Literature search
Search results
Impact of endometrioma on IVF/ICSI outcomes
Impact of endometriosis
Effect of surgical treatment in women with endometrioma to IVF/ICSI outcomes
Women with endometrioma have:• Similar LBR to women with no endometriosis
• (OR 0.98 95% CI [0.71, 1.36], 5 studies, 928 women, I2=0%) • Similar CPR to women with no endometriosis
• (OR 1.17 95% CI [0.87, 1.58], 5 studies, 928 women, I2=0%) • Lower mean number of oocytes retrieved than women with no
endometriosis• (MD -0.98 95% CI [-1.85, -0.10] 941 cycles, I2=65%)
Women with endometrioma who had surgical treatment have:• Similar LBR to those left untreated
• (OR 1.09 CI 95% [0.64, 1.86] 3 studies, 302 women, I2=49%)• Similar CPR to those left untreated
• (CI 0.97 [0.77, 1.21], 10 studies, 1411 women, I2=0%)• Similar mean number of oocytes retrieved to those left
untreated• (MD -0.32 [-0.71, 0.06] 6 studies, 837 cycles, I2=0%)
In women with DIE:• Similar CPR and similar mean number of oocyte retrieved when
compared to tubal or male subfertility• Women with surgically treated DIE have higher pregnancy rate (OR
2.19 [1.12,4.28], 1 study, 169 women) compared to women with conservative management
• Caution needs to be applied to the interpretation of results obtained from a single controlled study
Summary results
We searched all published and unpublished studies from 1980-2014. We included participants who had surgical management of endometrioma and/or DIE prior to ART. The quality of each paper was assessed and scored according to Newcastle-Ottawa Assessment scale. All suitable data were extracted and analysed using RevMan5
Methodology
Does surgery prior to Artificial Reproductive Treatment (ART) affect IVF/ICSI outcomes in women with endometrioma and/or deep infiltrating endometriosis (DIE)?
A result from meta-analysis and systematic review
Mukhri Hamdan1,2,3 Hany Arrifin2 Ying Cheong1,31The department of Human And Developmental Health University of Southampton, UK 2 Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia 3 Complete Fertility Centre, Southampton, UK
Tsoumpou I, Kyrgiou M, Gelbaya TA, and Nardo LG. (2009) Fertility & Sterility; 92 75-87Benschop L, Farquhar C, van der Poel N, and Heineman MJ. (2010) Cochrane Database Syst Rev; CD008571.Sallam HN, Garcia-Velasco JA, Dias S, and Arici A. (2006) Cochrane Database Syst Rev; CD004635.Vercellini P, Somigliana E, Vigano P, Abbiati A, Barbara G, and Crosignani PG. (2009) Hum Reprod; 24 254-69Meuleman C, Tomassetti C, D'Hoore A, Van Cleynenbreugel B (2011) Hum Reprod Update; 17 311-26.Keckstein J and Wiesinger H. (2005) Minim Invasive Ther Allied Technol; 14 160-6.Haas D, Chvatal R, Habelsberger A, Wurm P, Schimetta W, and Oppelt P. (2011) Fertil Steril; 95 1574-8.Donnez J and Squifflet J. (2010) Hum Reprod; 25 1949-58.
References
In women with DIE, those who had surgical resection of the lesion has higher pregnancy rate (OR 2.19 [1.12,4.28], 1 study, 169 women) compared to women with conservative management. The study also showed no difference in number of mean oocytes retrieved whether or not women with DIE have coexisting endometrioma.
Impact of surgical treatment in patient with DIE
Forest Plot 1.1: LBR of women with untreated endometrioma compared to those without endometriosis
Forest Plot 1.2: CPR of women with untreated endometrioma compared to those without endometriosis
Forest Plot 1.3: Mean number of oocytes retrieved from women with untreated endometrioma compared to those without endometriosis
Forest Plot 2.1: LBR of women with treated endometrioma compared to those with untreated endometrioma
Forest Plot 2.2: CPR of women with treated endometrioma compared to those with untreated endometrioma
Forest Plot 2.3: Mean number of oocytes retrieved from women with treated endometrioma compared to those with untreated endometrioma
Laparoscopic cystectomy vs Transvaginal aspiration of endometrioma
Participants must have had endometrioma and/or DIE diagnosed by laparoscopy or imaging tests such as ultrasound and magnetic resonance imaging. DIE is defined according to various accepted classifications (Meuleman 2011, Haas 2011 , Keckstein2005)
Type of participants
Studies were included if: They have participants with endometrioma and/or
DIE underwent IVF/ICSI Have at least one control group for comparison
whether or not they have received surgical treatment prior to IVF/ICSI
Type of studies
Impact of DIE on IVF/ICSI outcomes
Forest Plot 3.1: CPR of women with endometrioma who had laparoscopic cystectomy vs those who had trans-vaginal aspiration
Forest Plot 3.2: Mean number of oocytes retrieved from women with endometrioma who had laparoscopic cystectomy vs. those who had trans-vaginal aspiration
Women with endometrioma or DIE have similar IVF/ICSI outcomes compared to those without disease
There is no evidence of benefit for surgical treatment of endometrioma before ART
More studies are required to further elucidate if surgery prior to ART for women with DIE is beneficial, as surgery on this group of women is associated with a high complication rate (Donnez 2010)
Conclusions
Forest Plot 4.1: LBR of women with DIE compared to women with no DIE who underwent IVF/ICSI
Forest Plot 4.2: CPR of women with DIE compared to women with no DIE who underwent IVF/ICSI
33 StudiesType
• 31 Endometrioma• 1 DIE
• 1 Combination of both
Designs• 30 Non randomised
studies• 3 RCTs
Surgical intervention
• 20 have surgical intervention
• 13 no surgical intervention
Surgical approach• 31
Laparoscopic/laparotomy
• 2 Trans-vaginal procedures
Quality of studies
• Moderate and good quality
Laterality of disease• 3 unilateral• 6 bilateral
• 10 both unilateral/bilateral• 14 not specified
No difference in LBR in women with endometrioma compared to those with no endometriosis
No difference in CPR in women with endometrioma compared to those with no endometriosis
Lower number of oocytes were retrieved from women with endometrioma compared to those with no endometriosis
Similar LBR in women with treated endometrioma compared to those with intact endometrioma
Similar LBR in women with treated endometrioma compared to those with intact endometrioma
No difference in mean number of oocytes retrieved from women with treated endometrioma compared to those with intact endometrioma
No difference in LBR in women with endometrioma who had laparoscopic cystectomy compared to trans-vaginal aspiration
No difference in CPR in women with endometrioma who had laparoscopic cystectomy compared to trans-vaginal aspiration
No difference in LBR in women with DIE compared to those without DIE
No difference in CPR in women with DIE compared to those without DIE
Subgroups were created within included studies to compare those who has women with surgical intervention prior to IVF/ICSI compared to those who did not receive surgical intervention for endometrioma and DIE separately
Subgroup analysis