Prognostic factors of ovarian response and IVF outcome in patients with deep infiltrating endometriosis Claire GAUCHE-CAZALIS, Chadi YAZBECK Obstetrics Gynecology and Reproductive Medicine Department Bichat Claude Bernard University Hospital, Paris, France
Endometriosis & Infertility :10 years after Barnhart Clinical pregnancy after IVF (N=27) Harb et al. BJOG 2013 2
Endometriosis & Infertility Reduced fertility Impact on : Ovarian function and ovarian reserve Ovulation Cahill DJ, et al. Hum. Reprod. 1995., Cahill DJ, et al. Hum. Reprod. Update. 2000. Peritoneal function (inflammation) Implantation Lessey BA, et al. J Clin Endocrinol Metab, 1994. Oocyte and embryo quality D Hooghe TM et al. Semin. Reprod. Med. 2003. IVF outcome in women with deep endometriosis is still controversial, especially in those with previous surgery
Study Objectives Evaluate IVF outcome in infertile women after surgical treatment of deep endometriosis Evaluate prognostic factors of ovarian response and IVF outcome
Methods Retrospective cohort study: 82 patients with deep endometriosis (stages III-IV) surgically proved 82 control patients with tubal infertility without history of adnexal surgery (cystectomy and/or salpingectomy) Matched by age, stimulation protocol and recrutment time Time period interval 5 years: 2007-2012 Controlled ovarian hyperstimulation according to three main stimulation protocols: Long Short flare Antagonist IVF or ICSI according to sperm parameters First and second attempts of stimulation during the inclusion period
Patients characteristics: Surgery Lesion (n=82) Surgery (n=82) N % n/n % Ovary 54 65,85 cystectomy 41/54 75,92 unilatéral 31 37,80 1 24/54 44,44 bilatéral 23 28,05 2 17/54 31,48 Uterosacral ligament 34 41,46 Rectovaginal septum 20 24,39 sclerotherapy 13/54 24,07 14/34 41,18 8/20 40,00 Bowel 22 26,83 9/22 40,91 Bladder 6 7,32 4/6 66,67 Ureter 2 2,44 1/2 50,00 Douglas Obliteration 37 45,12 20/37 54,05 Laparoscopy: 88% 43,9% several surgeries 25,6% : 2 laparoscopies 8,5% : 3 laparoscopies Endometrioma mean diameter when surgery: 44,1mm Iteravitve cystectomy for 30% Time between surgery and ART: 2,33 years
Results: COH parameters Endometriosis Tubal factor p N % / ± DS Cycles number 159 128 Stimulation protocol N % / ± DS Long 117 79,59% 109 85,83% Short flare 24 16,33% 11 8,66% Antagonist 6 4,08% 7 5,51% Endometrioma at beginning of COH (<30mm) Fertilization technique : 52 32,70% 0 0 % IVF 80 50,31% 66 51,56% ICSI 78 49,69% 62 48,43% Mean stimulation duration (days) 10 ± 2,21 10,05 ± 1,50 0,69 Total FSH >3000 (IU) 36 28,13% 22 17,46% 0,04 Peak E2 level at hcg (pg/ml) 1810,1 ± 953,9 2223,4 ±1006,8 <0,001 Cycle cancellation rate 23 14,47% 2 1,60% <0,001 0,15 0,89
Results: COH outcome Endometriosis (n=159) Tubal factors (n=128) p Mean / n ± DS / % Mean / n ± DS / % Retrieved oocyte number 8,77 ± 5,98 9,68 ± 4,72 0,17 Oocyte retrieval 3 24 18,46% 10 7,81% 0,01 Total embryos obtained by cycle 4,57 ± 3,44 4,80 ± 3,20 0,56 Embryo transfert cancellation rate 19 11,95% 16 12,50% 0,89 Implantation rate (mean of %) 23,50 ± 3,42 22,84 ± 3,49 0,89 Pregnancy rate per cycle (%) 40/159 25,16% 39/128 30,47% 0,32 Cumulative pregnancy rate 74 46,54% 50 39,06% 0,20
Correlation between basal FSH and ovarian response FSH is weakly correlated to oocyte retrieval It is only significant among endometriosis patients. r=-0,34 ; p<0,001 r=-0,07 ; p=0,42
Correlation between basal AMH and ovarian response AMH is strongly correlated to the number of oocytes retrieved in the two groups. The correlation coefficient is better among endometriosis patients AMH is a better predictive factor than FSH for ovarian response r=+0,56 ; p<0,001 r=+0,48 ; p<0,001
Logistic regression model: Predictors of poor ovarian response to COH Predictors Ajusted OR* 95% CI Endométriosis III/IV 3,66 1,20 11,19 Without previous ovarian cyctectomy 2,27 0,59 8,76 With previous ovarian cyctectomy 5,65 1,44 22,12 Patients age (years) 1,24 1,06 1,46 Basal FSH (mui/ml) 0,96 0,77 1,20 Basal AMH (ng/ml) 0,62 0,39 0,97 Tubal infertility group was considered as the reference Poor responders were defined by total retrieved oocyte number 3 * Logistic model also ajusted for BMI, basal estradiol, total FSH dose and infertility type and duration
Conclusion Patients with surgically treated deep endometriosis are poor COH responders. Basal AMH level is a good biomarker of ovarian reserve and ovarian response in surgically treated endometriosis patients. In addition to age and basal AMH level, a significant prognostic factor for poor ovarian response was previous ovarian cystectomy. However, when an ovarian response to stimulation was obtained, the implantation and pregnancy rates were comparable to the control group.
Les études comparables à la notre Auteurs Azem (1999) Al Azemi (2000) Aboulghar (2003) Kuivasaari (2005) Matalliotakis (2007) Coccia (2011) Endo metri ose III-IV Tém oins Tubai res Ovocytes recueillis Implantation Grossesse cliniques par cycle (%) 58 60 7,1 9,0 Non évalué 10,6 22,4 0,001 40 80 6,9 7,1 NS Non évalué 62,6* 63,3* NS 85 177 4,5 10,7 <0,000 1 8,7 22,3 <0,001 15,3 52,5 <0,0001 67 87 8,7 9,3 NS 13,7 22,1 <0,005 22,6 36,6 <0,01 68 106 9,4 12,3 0,001 11,4 11,8 NS 27,8 29,8 NS 94 72 6,7 10,8 0,001 5,3 10,8 NS 7,3 22,5 0,006 Notre étude 82 82 8,8 9,7 NS 23,5** 22,8** NS 23,9 27,3 NS Taux de grossesse cumulée ** Moyenne des %