Endometrioma : what is the best option? Claudia Tosti, Errico Zupi

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1 Endometrioma : what is the best option? Claudia Tosti, Errico Zupi

2 Clinical symptoms Endometrioma Deep endometriosis Adenomyosis Ovarian reserve Bilateral endometrioma Previous surgery

3 American Society for Reproductive Medicine, Fertil Steril, 2008 Management of endometrioma Pain Infertility Surgical treatment Removal of lesions Adhesiolysis Medical treatment To block the growth or prevent the recurrences Infertility clinic Both medical and surgical treatments for endometriosis are effective and choice of treatment must be individualized

4 Management of endometrioma! The decision to proceed with surgery should be considered carefully if the woman has had previous ovarian surgery! In endometrioma-related infertility larger than 3 cm, there is no evidence that cystectomy prior to treatment with ART improves pregnancy rate! In endometrioma-related infertility, ART should be offered after surgery ESHRE 2014

5 Management of endometrioma! Surgical removal of endometrioma in infertile patients is recommended for those greater than 3 cm! There is no evidence that surgical treatment of endometriomas (by aspiration or cystectomy) improves success rates through IVF! Ovarian response might be reduced in some women who have undergone surgery for endometriomas JOGC 2010 Johnson NP et al Hum Reprod. 2013

6 Management of endometrioma Previous surgery Volume/Size Age Desire of pregnancy c Symptoms

7 Management of endometrioma No desire of pregnancy yrs With or Without pain yrs Pain <4 cm >4 cm Medical treatment Surgery

8 Management of endometrioma Desire of pregnancy yrs No pain yrs With or Without pain <4 cm >4 cm Surgery natural conception 1 year ART natural conception 6-12 months

9 Endometrioma and ovarian reserve Well-defined ovarian capsule! dermoids! serous cystadenomas! mucinous cystadenomas Ovarian tissue removed 6% Endometriomas (margin of ovarian tissue) Ovarian tissue removed 54-69% Endometrioma cyst wall Primordial follicles Muzii L et al, J Am Assoc Gynecol Laparosc. 2004

10 Endometrioma and ovarian reserve Ovarian reserve: number and quality of the follicles left in the ovary Clinical markers! Age Serum markers! FSH, E2! AMH US markers! Ovarian volume! Antral follicle count de Carvalho BR. et al, ISRN Obstet Gynecol, 2012

11 Endometrioma and ovarian reserve Decreasing AMH after surgery are influenced by: Surgical tecnique Age Bilateral/unilateral localization AFS score Hwu et al, Reprod Biol Endocr, 2011 Hirokawa W. et al, Hum Reprod, 2011

12 AMH (ng/ml), mean SD <.001 Basal FSH (miu/m)l, mean SD <.001 Total AFC (n), median (range) 8 (4 15) 6.5 (4 13).34 AFC in the healthy ovary (n), median (range) 5.5 (3 9) 5.5 (4 12).65 AFC in the affected ovary (n), median (range) 2 (1 6) 1 (0 4).005 Volume of the affected ovary (cm 3 ), mean SEM <.001 Volume of the healthy ovary (cm 3 ), mean SEM Ferrero et al., Fertil Steril (2015) Endometrioma and ovarian reserve and repetitive surgery Muzzi et al., Fertil Steril (2015) First surgery for OMA Recurrent surgery for Oma P value (n = 17) (n = 11) *: p value (operated versus controlateral ovary) Cyst wall thicknes 1.1 ± ± Antral follicule count * Ovarian volume* Variable Before second surgery (n [ 18) After second surgery (n [ 18) P value

13 Endometrioma and ovarian reserve Ovarian cystectomy for endometriomas seems to cause significant damage to ovarian reserve with up to 40% fall in serum AMH concentration Raffi F et al, J Clin Endocrinol Metab 2012

14 Endometrioma and ovarian reserve Evidence deriving from the evaluation of serum AMH level modifications after surgical excision of endometriomas supports a surgery-related damage to ovarian reserve! Further evidence to confirm this result does not seem to be a research priority Somigliana E et al, Fertil Steril 2012

15 American Society for Reproductive Medicine, Fertil Steril, 2008 Management of endometrioma Pain Infertility Surgical treatment Removal of lesions Adhesiolysis Medical treatment To block the growth or prevent the recurrences Infertility clinic

16 Endometrioma in infertile women undergoing ART: remove it or not? surgery for endometriomas does not improve the outcome of ART surgery for endometriomas may damage ovarian reserve the majority of gynaecologists in the UK offer ovarian cystectomy Raffi F et al, Hum Reprod. 2012

17 Management of endometrioma before IVF Endometrioma in infertile women undergoing ART: remove it or not? 95% offer surgery (cistectomy) for endometriomas before ART 26% offer surgery even for small endometrioma (<5cm)! Should reconsider the value of surgery, especially in patients who have no or mild symptoms Raffi F et al, Hum Reprod. 2012

18 Endometrioma in infertile women undergoing ART: remove it or not? Almog B et al, Fertil Steril 2012

19 Endometrioma in infertile women undergoing ART: remove it or not? Laparoscopic cystectomy for ovarian endometriosis does not offer any additional benefit in terms of fertility outcomes 1. The quality of the oocytes retrieved in IVF cycles is not improved after surgery 2. Patients going through an operative procedure might extend the time to pregnancy Garcia-Velasco JA. et al. Fertil Steril, 2004 Garcia-Velasco JA. et al. Curr Opin Obstet Gynecol. 2012

20 Endometrioma in infertile women undergoing ART: remove it or not? Diminished ovarian reserve AMH < 2ng/ml Retrospective study OMA Cystectomy Idiopathic Characteristics Group A (125 cycles) Group B (243 cycles) P-value... Implantation rate (%) 13/181 (7.2%) 49/364 (13.5%) 0.03 Clinical pregnancy rate per cycle (%) 14/125 (11.2%) 50/243 (20.6%) 0.02 Live birth rate (%) Per cycle 9/125 (7.2%) 41/243 (16.9%) 0.01 Per transfer 9/104 (8.7%) 41/216 (18.8%) 0.02 Spontaneous abortion rate (%) (before or after 12 weeks of gestation) 4/13 (30.8%) 8/49 (16.3%) NS Ectopic pregnancy rate (%) 1/14 (7.1%) 1/50 (2.0%) NS Multiple pregnancy rate (%) 2/13 (15.4%) 6/49 (12.2%) NS Roustan et al., Hum Reprod (2015)

21 Endometrioma in infertile women undergoing ART: remove it or not? Item Theoretical Demonstrated Effect of prophylactic relevance clinical relevance surgery... Ovarian responsiveness ++ 2 Detrimental Oocytes competence ++ 2 Ineffective Technical difficulties + 2 Doubtful Endometrioma rupture + 2 Effective Injury to adjacent organs ++ 2 Doubtful Infection of the endometrioma ++ + Effective Follicular fluid contamination with the endometrioma content + +/2 Effective Progression of endometriosis ++ 2 Effective Pregnancy complications ++ +/2 Doubtful Occult malignancy missed Effective Cancer development after IVF Effective! No systematic surgery before IVF Somigliana, et al., Human Reprod Update (2015)

22 Should we, or should we not, operate on endometriomas in patients scheduled for ART? Outcomes from ART were not affected by the time interval between surgery and ART Falcone T. et al. J Reprod Med, 2008 After surgery, couples must attempt to conceive naturally for at least 1 year, in women younger than 35 years If this attempt fails, it is recommended to go directly to ART De Ziegler D. et al, Lancet 2010 Falcone T. et al. Semin Reprod Med, 20

23 American Society for Reproductive Medicine, Fertil Steril, 2008 Management of endometrioma Pain Infertility Surgical treatment Removal of lesions Adhesiolysis Medical treatment To block the growth or prevent the recurrences Infertility clinic

24 When a medical treatment is required for endometrioma? 1 When surgery is controindicated or refused 2 When there is no desire of pregnancy 3 To prevent or treat recurrence Practice Committee of the American Society for Reproductive Medicine. Fertil Steril 2008

25 m eat c a l tr i d e M Medical treatment in endometrioma-associated infertility s estin -prog Estro s estin l, NETA) Prog zo a t, dan oges (dien + ents:) reatm t l) a n ormo s) Non:h NSAID ) a eg :3 Om ferrin) t c o La Medical therapy as ovarian suppression for stage I or II endometriosis does not improve fecundity rates and should not be offered ESHRE Guideline, Hum Reprod Medical suppressive therapy does not influence fertility and delays conception Fecundity does not rebound on termination Post-operative medical treatment has no benefits in cases of infertility Lebovic DI. et al. Obstet Gynecol, 201 De Ziegler D. et al, Lancet 2010

26 When a medical treatment is required for endometrioma? Pre-operative suppression of ovarian function for 6 months reduces endometriosis-associated pain Medical treatment is effective, but symptoms tend to recur rapidly after therapy is stopped! not affect the primary mechanisms responsible for the disease! temporary reduction of increase in size of the lesions Falcone T et al. Semin Reprod Med, 2011

27 When a medical treatment is required for endometrioma? Post-operative E/P use significantly reduces the recurrence of ovarian endometrioma and symptoms within 2-3 years following laparoscopic excision OC for at least 12 months OC for less of 12 months Vercellini P et al. AJOG, % 40% 35% 30% 25% 20% 15% 10% 5% 0% recurrency continuous users cyclic users ever used E/P discontinued used E/P never used E/ P nonusers Takamura M. et al. Hum Reprod, 2009 Seracchioli R et al. Fertil Steril, 2010

28 When a medical treatment is required for endometrioma? Dienogest 1. First-line treatment for pain in case of: " endometrioma " peritoneal endometriosis " deep infiltrating endometriosis 2. Pre-surgical treatment 3. Post-surgical treatment

29 Medical indication for fertility preservation Elizur SE et al, Fertil Steril 2009 Preoperative fertility preserving measures such as oocyte or embryo cryopreservation could be offered in as part of the treatment strategy to young women who require extensive ovarian surgery for severe endometriosis-related pain Streuli I et al, Hum Reprod 2012

30 Management of endometrioma Diagnosis 1 level Medical chart (pain) AMH 2D-3D ultrasound 2 level MRI Infertility clinic Outpatient clinic Hysterosalpingography PMA Medical treatment Surgery Laparoscopic surgery for OMA Follow-up

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