Chloé Maignien, Resident

C. Maignien, P. Santulli, D. Korb, L. Marcellin, V. Gayet, V. Blanchet, J. Gonnot, D. de Ziegler, C. Chapron

Université Paris Descartes, Sorbonne Paris Cité, Faculté de médecine, AP-HP,

Cochin Saint Vincent de Paul, Department of Gynecology Obstetrics II and Reproductive Medicine, Paris, France

Inserm, Unité de recherche U1016 – équipe Pr F. Batteux, Institut Cochin, Paris,

France

SEUD 2015

Society Of Endometriosis

and Uterine Disorders

Prognostic factors of ART outcome in a continuous series of 359 endometriosis patients

Endometriosis and IVF : conflicting evidence in the literature

Hamdan et al. Obstet Gynecol (2015)

Barbosa et al. Ultrasound Obstet Gynecol (2014)

Stage I/II vs controls

Stage III/IV vs controls

Live birth (OR, 95% CI)

0.96 (0.82 - 1.12) 0.77 (0.64 – 0.92)

Clinical pregnancy (OR, 95% CI)

0.84 (0.69 – 1.03) 0.60 (0.44 – 0.81)

Endometriosis and IVF : conflicting evidence in the literature

Why?

OMA SUP DIE

SUP = superficial endometriosis; OMA = endometrioma; DIE = deep infiltrating endometriosis

Implantation theory

Impact of surgery ?

Heterogeneous populations

Impact of adenomyosis ? !  Benaglia et al. (2014): similar implantation

rates !  Vercellini et al. (2014): negative impact on

clinical pregnancy and implantation Benaglia et al. Reprod Biomed Online (2014)

Vercellini et al. Human Reprod (2014)

Objective of the study

To evaluate the IVF/ICSI outcomes in a continuous series of endometriosis

(OSIS) patients

- Clinical pregnancy

rates - Live birth

rates

Outcomes according to

the PHENOTYPE

Prognostic factors of

ART outcomes

Methods (1)

TVS = transvaginal sonography; MRI = magnetic resonance imaging; USL = uterosacral ligament

June 2005 February 2013 Observational cohort study

SUP

OMA

DIE: -  USL

-  Vagina -  Bladder

-  Intestine -  Ureter

Severity

359 OSIS patients

Previous surgery for OSIS

Histological diagnosis

No history of surgery "

Imaging criteria (TVS, MRI)

Radiological diagnosis

Methods (2)

Controlled Ovarian Hyperstimulation IVF/ICSI

General characteristics:

# Age # Weight # Height # BMI # Gravidity # Parity # Previous surgery for OSIS and/or OMA

Outcomes :

# Number of oocytes # Number of embryos obtained/tranfered # Clinical pregnancies #  Live birth

Infertility work-up:

#  Duration of prior infertility

#  Hysterosalpingography #  Cycle day 3 level measurement of FSH,

LH, E2, AMH #  Antral follicle count

(AFC) #  Semen analysis #  Adenomyosis

YES NO

Pregnancy

E2 = estradiol

OSIS phenotype

Baseline characteristics Lesion topography

N = 359

DIE 212 (59.1%) USL 67 (31.6%)

Vagina 10 (4.7%) Bladder 11 (5.2%) Intestine 118 (55.7%) Ureter 6 (2.8%)

SUP 49 (13.6%)

OMA 98 (27,3%)

R 30 (30.6%) L 36 (36.7%) BI 32 (32.7%)

ADENOMYOSIS

145 (40.4%)

ENDOMETRIOSIS

R = right; L = left; BI = bilateral

Baseline characteristics Global population

Characteristics n = 359

Age (years) 33.4 ± 4.0

BMI (kg/m2) 22,5 ± 3,5 Nulligravida (n, %) 259 (72.1%)

Nullipara (n, %) 315 (87.7%)

Duration of prior infertility (years)

4.0 ± 2.2

Type of infertility (n, %) - Primary - Secondary - Associated male factor - Associated tubal factor

277 (77.2%) 82 (22.8%) 67 (18.7%) 38 (10.5%)

Previous surgery (n, %) - For OSIS - For OMA

279 (77.7%) 170 (47.4%)

Mean ± Standard Deviation

Pregnancies Global IVF outcomes

Outcomes GLOBAL POPULATION (n = 359)

Number of cycles 720

Number of embryo transfers 500

Number of pregnant women 158 (44%)

Number of live birth 114 (31.8%)

Clinical pregnancy rate per cycle 25.3%

Clinical pregnancy rate per embryo transfer

36.4%

Implantation rate 22.7%

Live birth rate per cycle 15.8%

Live birth rate per embryo transfer 22.8%

Baseline characteristics according to the OSIS phenotype

Characteristics SUP (n = 49)

OMA (n = 98)

DIE (n = 212)

p -value

Age (years) 33.9 ± 3.6 34.1 ± 4.1 33.0 ± 4.0 0.058 BMI (kg/m2) 22.6 ± 3.7 22.0 ± 3.4 22.8 ± 3.6 0.244

Gravidity 0.5 ± 1.0 0.4 ± 0.7 0.4 ± 0.8 0.558

Parity 0.1 ± 0.3 0.1 ± 0.4 0.1 ± 0.4 0.658

Associated male F. 9 (18.4%) 25 (25.5%) 67 (18.7%) 0.113

Associated tubal F. 5 (10.2%) 6 (6.1%) 38 (10.5%) 0.212

Day 3 FSH (IU/L) 8.3 ± 5.4 7.8 ± 2.9 7.5 ± 4.4 0.554

AMH (ng/mL) 2.8 ± 1.8 3.1 ± 2.6 2.6 ± 2.1 0.281

AFC 14.0 ± 8.0 12.0 ± 6.2 11.0 ± 6.4 0.041

Adenomyosis 7 (14.3%) 18 (18.4%) 120 (56.7%) < 0.001

Previous surgery for OSIS

47 (95.9%) 79 (80.6%) 153 (72.2%) 0.212

F = factor

Pregnancies Outcomes according to the OSIS phenotype

SUP (n = 49)

OMA (n = 98)

DIE (n = 212)

p-value

Number of cycles 95 200 425

Cancellation rate 18.9% 29.5% 33.6% 0.018

Clinical pregnancy rate per cycle

30.5% 27.5% 23.1% 0.22

Clinical pregnancy rate per embryo transfer

37.7% 39% 34.8% 0.67

Implantation rate 25% 23.4% 21.6% 0.66

Abortion rate 55.2% 40% 30.6% 0.049

Live birth rate per cycle 13.7% 16.5% 16% 0.82

Live birth rate per embryo transfer

16.9% 23.4% 24.1% 0.40

Prognostic factors of ART outcomes Univariate analysis

Characteristics Women who didn’t became pregnant

Women who became pregnant

p -value

Age > 35 years 90 (44.8%) 54 (34.1%) 0.042 BMI (kg/m2) 22.8 ± 3.7 22.2 ± 3.4 0.174

Gravidity 0.4 ± 0.9 0.3 ± 0.7 0.247

DIE 129 (64.2%) 83 (52.5%) 0.026

Number of DIE lesions 1.2 ± 1.3 0.7 ± 1.0 < 0.001

Intestinal DIE 88 (43.8%) 36 (22.8%) < 0.001

Day 3 FSH (IU/L) 8.4 ± 5.2 6.8 ± 2.2 < 0.001

AMH < 2 ng/mL 103 (51.2%) 42 (26.6%) < 0.001

AFC < 10 101 (50.2%) 43 (27.2%) < 0.001

Associated Adenomyosis 91 (45.3%) 54 (34.2%) 0.033

Previous surgery for OSIS 171 (85.1%) 108 (68.4%) < 0.001

Previous surgery for OMA 108 (53.7%) 62 (39.2%) 0.006

Prognostic factors of ART outcomes Multivariate analysis

OR (95% CI ) p - value

AMH < 2 ng/mL 0.49 (0.3-0.9) 0.014

AFC < 10 0.41 (0.2-0.7) 0.002

Previous surgery for OSIS 0.29 (0.1-0.6) 0.001

Previous surgery for OMA 0.34 (0.2-0.7) 0.002

Intestinal DIE 0.31 (0.2-0.6) < 0.001

Conclusion

! IVF outcomes did not differ according to the phenotypes

! Prognostic factors associated with poorer outcomes

Intestinal DIE

Altered ovarian reserve : •  AMH < 2 ng/mL •  AFC < 10

Associated adenomyosis

Previous surgery for OSIS/OMA

Gynecology Surgical unit: C Chapron, B Borghese, P Santulli,

H Foulot, MC Lafay-Pillet, A Bourret, G Pierre, M Even, MC Lamau, L Marcellin, P Marzouk Medical unit: A Gompel, G Plu-Bureau, L Maitrot

Reproductive Endocrinology unit: D de Ziegler, P Santulli, V Gayet, P Piertea, FX Aubriot

Intestinal surgery B Dousset, S Gaujoux, M Leconte

Radiology AE Millischer, L Maitrot

Laboratory: Genetic D Vaiman, F Mondon, S Barbaux

Laboratory: Imunulogy

F Batteux, S Chouzenoux C Nicco, C Chéreau, B Weill

Laboratory: Reproductive biology

JP Wolf, V Lange, K Pocate, JM Kuntzman, C Chalas

Statistical unit

F Goffinet, PY Ancel

D. de Ziegler, Professor and Head, Reproductive Endocrinology and Infertility unit, A. Gompel, Professor and Head, Medical Gynecological unit,

C. Chapron, Professor and Chair, Gynecology Obstetrics II and Reproductive Medicine