Evidence-based management of endometriosis-associated infertility Hassan N. Sallam, MD, FRCOG, PhD (London) Professor in Obstetrics and Gynaecology The University of Alexandria, and Clinical and Scientific Director, Alexandria Fertility Center, Alexandria, Egypt 3rd Congress of Society of Reproductive Medicine, 5 – 9 October 2011, Antalya / Turkey
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Evidence-based management of endometriosis-associated infertility Hassan N. Sallam, MD, FRCOG, PhD (London) Professor in Obstetrics and Gynaecology The.
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Evidence-based management of endometriosis-associated
infertilityHassan N. Sallam,
MD, FRCOG, PhD (London)Professor in Obstetrics and Gynaecology
The University of Alexandria, andClinical and Scientific Director,
Alexandria Fertility Center, Alexandria, Egypt
3rd Congress of Society of Reproductive Medicine, 5 – 9 October
Hughes et al, Cochrane Database Syst Rev. 2007 Jul 18;(3):CD000155
Effect of letrozole on the ASRM score (OS)
Ailawadi et al, Fertil Steril 81(2): 290-6, 2004
Letrozole for the treatment of endometriosis (RCT)
Letrozole
(n = 47)
Triptorelin
(n = 40)
Controls(n = 57)
P value
CPR after 12 months
23.4%27.5%28.1%NS
Recur-rence
6.4%5%5.3%NS
Alborzi et al, Arch Gynecol Obstet 284: 105-10, 2011
Novel medical therapies
1. Antiangiogenic agents (Dabrosin et al, 2002)
2. SPRMs (e.g. J867) (Chwalisz et al, 2002)
3. GnRH antagonists (e.g. ganirelix and cetrorelix) (Kupker et al, 2002)4. Mifepristone (Murphy et al, 2002)5. Local therapy (e.g. methotrexate)
(Mesogitsis et al, 2000)
Management of endometriosis-associated
infertility
1. Surgical treatment 2. Medical treatment
3. Combined medical and surgical therapy 4. Controlled ovarian hyperstimulation +/-
IUI5. Assisted reproductive techniques
Pre-operative medical treatment for endometriosis (CCT)
Danazol Gestrinone Buserelin
Regression of endometriosi
s
30%34% 73% *
Cumulative pregnancy
rate
45%47%58% *
Donnez et al, Int J Fertil 35(5): 297-301, 1990
Post-operative GnRHa for endometriosis
(Cumulative pregnancy rates - CPR)
Surgery with
GnRHa
Surgery without GnRHa
P valu
e
Parazzini et al, 1994
(RCT)
19%18%NS
Vercellini et al, 1999
(RCT)
11.6%18.4%NS
Pre and post operative medical therapy for endometriosis surgery
(Cochrane review)
• Pre-surgical medical therapy showed a significant improvement in AFS
scores• Post-surgical hormonal suppression showed no benefit for the outcomes
of pain or pregnancy rates but a significant improvement in disease
recurrenceYap et al, Cochrane Database Syst 2004;
(3):CD003678
Management of endometriosis-associated
infertility
1. Surgical treatment 2. Medical treatment
3. Combined medical and surgical therapy
4. Controlled ovarian hyperstimulation +/- IUI
5. Assisted reproductive techniques
COH in stages I & II endometriosis
Intervention
No therapy
COHP value
Simpson et al, 1992 (CCT)
Clomiphene citrate
9%22%<0.05
Fedele et al, 1992
(RCT)
HMG24%37.4%
NS
COH + IUI in stages I & II endometriosis
No therapy
COH + IUIP value
Deaton et al, 1990 (RCT)
3.3%9.5%<0.05
Tummon et al, 1997 (RCT)
2%11%<0.005
Serta et al, 1992 (CCT)
32%32%NS
Peterson et al, 1994 (CCT)
1.4%15%<0.005
COH + IUI in endometriosis (Meta-analysis)
Number of studies
Number of cycles
Mean cycle fecundity (SD)
Stage I & II57830.14 *
Stage III & IV
31790.08
Peterson et al, Fertil Steril 62(3):535-44, 1994
Management of endometriosis-associated
infertility
1. Surgical treatment 2. Medical treatment
3. Combined medical and surgical therapy
4. Controlled ovarian hyperstimulation +/- IUI
5. Assisted reproductive techniques
Intracytoplasmic sperm injection (ICSI)
IVF in endometriosis versus tubal infertility (CPR)
Barnhart et al, Fertil Steril 77(6): 1148-55, 2002
Surgical approaches to treat endometriosis before IVF and
ICSI
1. Surgical removal of endometriomas appears to diminish the success rate of
IVF/ICSI (Aboulghar et al, 2003)2. Laparoscopic cystectomy has no
effect (Canis et al, 2001; Marconi 2002)
Surgical approaches to treat endometriosis before IVF and ICSI
(cont…)3. LASER vaporization of the internal
wall of endometriomas did not affect the outcome (Donnez et al,
2001; Wyns et al, 2003)4. Ultrasound-directed cyst
aspiration is associated with mixed results (Dicker et al, 1991;
Suganuma et al, 2002) and an increased incidence of infection (Nargund and Parsons, 1995)
Medical approaches to treat endometriosis before IVF and ICSI
1. Corticosteroids (Kim et al, 1997) (RCT but small and not repeated)
2. Danazol (Tei et al, 1998) (RCT but small and not repeated)
3. GnRH agonists (Oehninger et al, 1989; Dicker et al, 1990; Dale et al, 1990; Nakamura et al, 1992; Curtis et al, 1993; Marcus et al, 1994; Chedid et al, 1995; Ruiz-
Velasco and Allende, 1998)
Corticosteroids before IVF in endometriosis (RCT)
Corticosteroids
(n = 54)
Controls
(n = 57)
P value
CPR42.6%22.8%<0.05
Miscarriage rate
21.7%15.4%NS
Multiple pregnancy
rate
17.4%15.4%NS
Kim et al, J Obstet Gynaecol Res 23(5): 463-70, 1997
Danazol before IVF in repeated IVF failures (RCT)
Danazol (400 mg/d for 12
wks)
Controls
P value
Number4141
CPR40%19.5%<0.05
Tei et al, J Reprod Med 43(6): 541-6, 1998
Sallam et al, Cochrane Database Syst Rev 25;(1):CD004635, 2006
GnRH agonist v/s no agonist before IVF
(Clinical pregnancy rate per woman)
Sallam et al, Cochrane Database Syst Rev 25;(1):CD004635, 2006
GnRH agonist v/s no agonist before IVF
(Ongoing pregnancy rate per woman)
Sallam et al, Cochrane Database Syst Rev 25;(1):CD004635, 2006
GnRH agonist v/s no agonist before IVF (Number of oocytes
retrieved)
Sallam et al, Cochrane Database Syst Rev 25;(1):CD004635, 2006
GnRH agonist v/s no agonist before IVF (Dose of HMG or FSH
required)
Sallam et al, Cochrane Database Syst Rev 25;(1):CD004635, 2006