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