Managing infertility when adenomyosis and endometriosis co-exist

Transcription

1 Managing infertility when adenomyosis and endometriosis co-exist Jinhua Leng Beijing,China

2 Endometriosis Endometriosis (EM) is a common, benign, ovary hormone-dependent gynecologic disorder which affects mainly reproductive-age women Endometriosis is considered to be responsible for infertility and pelvic pain May affect 10% of women of reproductive age Three types of pelvic endometriosis Peritoneal Endometriosis Ovarian Endometrioma Deeply Infiltrating Endometriosis (DIE)

3 Adenomyosis Adenomyosis (AD) is defined by the presence of endometrial glands and stroma in the myometrium Prevalence: varies significantly between studies (from 5% to 70%), generally underestimated Most frequent symptoms: dysmenorrhea, abnormal uterine bleeding, etc. Two types: diffuse form, focal form

4 PEM DIE OEM AD+EM

5 Macroscopic and microscopic appearance of AD

6 MRI Features of AD focal and diffuse

7 Prevalence of EM in patients with AD Author Adenomyosis N Endometriosis N(%) Leng JH et al.(2011) 72(histology) 24(33.3%) Di Donato et al. (2014) 217(ultrasound) 165(76.0%) Chapron et al. (2017) 175(MRI) 153(87.4%) Leyendecker et al. (2015) 67(MRI) 54(80.6%) Em and AD often coexist Several authors reported the prevalence of EM in patients with AD. Our study showed in 72 histologically diagnosed AD, 33.3% had concomitant EM. Chapron and another 2 authors reported in US/MRI diagnosed AD, 76-87% had coexistant EM

8 What is the relationship between endometriosis phenotypes and adenomyosis? EM subtype N Diffuse form Focal form PEM 40 8(20.0%) 3(7.5%) OEM 31 14(45.2%) 6(19.3%) DIE (35.5%) 110(66.3%) Surgery findings of 175 preoperatively MRI diagnosed AD and histologically diagnosed of EM Among EM women, diffuse AD had no correlation with EM phenotypes. In contrast, focal AD was correlated significantly with EM phenotype Study summary: Focal adenomyosis located in the outer myometrium (FAOM) was observed more frequently in women with endometriosis, and was significantly associated with the DIE phenotype Chapron et al. Hum Reprod. 2017

9 Prevalence of AD among EM patients data from China A retrospective study including 10,579 patients who had undergone surgery for endometriosis from The prevalence of AD among EM patients significantly increased with age: Leng JH et al. Chin Practical Obs Gyn, 2011, 27(3):188 30y 30-40y 40-50y >50y P AD 5.5% 22.4% 52.5% 70.8% A retrospective study of 600 patients who had undergone laparoscopic surgery for ovarian endometrioma from 2003 to 2008 OEM+AD group: Leng JH et al. Chin Practical Obs Gyn (2009) 15.5% of all patients with ovarian endometrioma older age: 35y 64.2%; higher infertility rate 20.8% vs 10.7% lower pregnancy rate after surgery:1/9(11.1%) vs 19/52 (36.5%)

10 Demographic data and symptoms of AD with and without EM Woman with AD+DIE were younger, more frequently nulliparous and have a history of previous surgery, with severe pain symptoms. While, women with AD alone represented the older age (37yrs vs 34yrs) and associated with AUB Nadine Di Donato N et al. (2014)

11 Impact on fertility 30 50% of women with endometriosis have infertility Women with mild endometriosis have a significantly lower probability of pregnancy than women with unexplained fertility (3 year pregnancy rate 36% vs 55%) IVF studies have suggested that women with more advanced endometriosis have poor ovarian reserve, low oocyte and embryo quality, and poor implantation rate Adenomyosis is an independent cause of infertility among women with EM The rates of implantation, clinical pregnancy rate, and live birth rate among women with AD were significantly lower than in those without The miscarriage rate in women with AD was higher than in those without Adenomyosis, in addition to EM, may further impact on reproductive outcome. This remains a subject of discussion

12 Pathogenesis of infertility Altered Endometrial Function and Receptivity Aberrant Endometrial Metabolism Steroid and their receptors) Altered Uterine Oxidative Stress Environment Impaired Implantation (Adhesion Molecules/ Implantation Markers/ Gene for Embryonic Development) Uterine Junctional Zone (JZ) JZ thickness (MRI) is the best negative predictive factor of implantation failure ---- Piver et al. Abnormal Uterotubal Transport Intrauterine Abnormalities Disturbed Uterine Peristalsis and Sperm Transport Destruction of Normal Myometrial Architecture and Function Effect on Gametes and Embryo Altered ovulation and oocyte production Luteal phase disruption Peritoneal fluid Inflammatory effects + increased activated macrophages damage the oocytes, sperm and embryo

13 Recommendation for infertility associated with EM NICE 2017 ESHER 2014

14 Endometriosis and infertility treatment Chinese guideline (2015) 1.Endometriosis collaborative group of obstetrics and gynecology branch of Chinese medical association, Chinese Journal of Gynaecology and Obstetrics, 2015, 50(3):1-9. Endometriosis and infertility Perform examination and fertility assessment according to the diagnosis and treatment path of infertility Laparoscope-hysteroscope surgery Endometriosis confirmation, staging, lesion resection and tubal function assessment Relapse type of endometriosis or diminished ovarian reserve Endometriosis at Stage I-II, EFI score 5 Moderate to severe (Stage III-IV) Age > 30 years, infertility or deep infiltrating duration> 3 years, with moderate endometriosis to severe male factors Age > 35 years, EPI 4 points, with severe male factors Expecting treatment Not pregnant in half year COH/IUI Not pregnant in 3 4 cycles IVF - ET

15 How to manage infertility when AD and EM co-exist? Conservative surgery Medication (GnRHa) ART (IVF/ICSI) Evidence and protocol for endometriosis-related infertility are relatively well established. But so far, limited data are available concerning the efficacy of different treatment options for adenomyosis or coexisting EM and AD on fertility outcomes. Treatment options include conservative surgery, medication and ART, or combined treatment.

16 Reproductive Outcomes of Fertility A systematic review about fertility-sparing surgery, including 18 studies and 1,396 infertile women with focal and diffuse adenomyosis Adenomyosis mean pregnancy % miscarriage % uterine rupture % preterm birth % focal diffuse Reproductive outcome appeared to be better in the focal AD group following surgery compared to the diffuse AD group. A higher incidence (6.8%) of uterine rupture was reported after surgery for diffuse AD. Tan J et al. (2018)

17 Reproductive Outcomes or focal vs diffuse adenomyosis. (a) Total (b) Natural conception vs ART 70 a) b) Reproducave outcome rate (%) 52, ,5 52,7 43,5 21,1 34, ,7 Pregnancy rate (%) ,7 18,2 0 Focal Pregnancy adenomyosis rate(%) Miscarrage rate(%) Successful Diffuse delivery adenomyosis rate(%) 0 Natural Concepaon Focal adenomyosis 0 ART Diffuse adenomyosis

18 Reproductive outcomes following surgery alone vs combined surgery & medical treatment for women diffuse and focal adenomyosis 70 Pregnancy rate(%) Successful delivery rate(%) Miscarrage rate(%) 67,1 61,3 Reproducave outcome rate (%) 52, ,5 38,5 31,3 16,2 17,6 9,8 33,3 31,3 23,8 19,6 49,1 38,6 27,6 11,6 54,8 45,1 21,8 0 Surgery alone n=96 Surgery&Medical (n=51) Diffuse All (n=147) Surgery alone n=165 Surgery&Medical (n=76) Focal All (n=241)

19 What are the problems of conservative surgery for AD? Complete resection of the lesion impossible Removal of healthy myometrial tissue inevitable Difficult to repair uterine defect Poor healing of the scar Decreasing the tensile strength of the uterus Increasing the risk of uterine rupture during pregnancy or labour Uterine Rupture is the most severe problem in perinatal management 6% after AD surgery vs 0.26% (myomectomy) vs 0.005% (non-scarred uterus ) Surgery should be performed only in selected patients who have severe pain symptoms, failed medical treatment and IVF or who has focal type of adenomyosis. Less rupture in laparotomy with surgical scapel than that in laparoscopy. If surgery is indicated, laparotomy is the surgery of choice for local AD patients with fertility desire

20 What is the role of resection of DIE on fertility outcome when DIE and AD coexist A systematic review and meta-analysis to evaluate fertility outcome of surgery for DIE, when adenomyosis coexists with DIE. AD was never excised. Result: DIE with adenomyosis: 7/59 (11.9%) conceived DIE without adenomyosis: 74/172 (43.0%) conceived Suggestion: women with DIE and concomitant adenomyosis should be informed that surgery may not have an appreciable effect on the likelihood of conception and that the same or possibly better chances of pregnancy could be obtained through IVF/ICSI Vercellini P et al. (2014)

21 Medical Treatment and reproductive outcome Some beneficial effect for fertility of GnRHa therapy in AD Tasuku Harada et al. (2016)

22 Effect of AD on IVF outcome Adenomyosis reduces pregnancy rates in infertile women undergoing IVF N Clinical pregnancy % Ongoing pregnancy % Miscarriage % AM Non-AM Salim R et al. (2012)

23 Fertility outcome of IVF pretreated with GnRHa Two retrospective studies compared infertile women with AD treated with long-term use of GnRHa before IVF Results: Long-term GnRHa treatment before IVF-ET/FET might improve pregnancy outcomes in women with adenomyosis Before IVF/ ICSI Pregnancy % Implantation % Ongoing pregnancy % stimulation duration(d) dose of gona- Dotropin (IU) retrieved oocytes* clinical pregnancy rate 194 with GnRHa 145 without GnRHa with GnRHa 11.5±2.1 3,421±1, ± % 116 without GnRHa 9.9±2.0 2,588±1, ± % Niu et al. (2013) Park et al. (2016)

24 Fertility outcome IVF vs Surgery Pregnant rate after in vitro fertilization (11-40%, total 32%) Pregnant rate after cyto-reductive surgery (total 47%) After surgery, the delivery rates and PR were only slightly higher than in women with AD who underwent IVF/ICSI Margit D et al. (2017)

25 EM+AD+infertility Clinical evaluation (PE/USG/MRI) and fertility evaluation AD with OEM DIE with AD OEM or other infertility related surgical indications Surgery: EM excision and fertility evaluation OEM recurrence or DOR No Severe pain symptom Or failed IVF Yes GnRHa & expectation Failed Diffuse AD GnRHa+IVF Repeatedly failed Focal AD Adenomyoma resection DIE resection

26 Summary Adenomyosis is frequently found in patients with endometriosis Co-existence of AM and EM may have a significant impact on fertility, which may lead to worse reproductive outcome compared with endometriosis alone Evaluation of co-existing adenomyosis in infertile patient with EM, especially DIE, is required GnRHa appear to be beneficial in improving pregnancy rates. Pretreatment with GnRHa may improve fertility outcomes The benefits on fertility of preserving surgery vary greatly: Surgery should be performed only in selected patients who have severe pain symptoms, failed medical treatment and IVF or who have focal type of adenomyosis

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