Ovulation suppression for endometriosis.
BACKGROUND
Endometriosis is the finding of endometrial glands or stroma in sites other than the uterine cavity. Endometriosis appears to be an oestrogen dependent condition. This hormonal dependency has prompted the therapeutic use of ovulation suppression agents, in an effort to improve subsequent fertility.


OBJECTIVE
To assess the effectiveness of ovulation suppression agents, including danazol, progestins and oral contraceptives, in the treatment of endometriosis-associated subfertility in improving pregnancy outcomes including live birth.


METHODS
We searched the Cochrane Menstrual Disorders and Sub-fertility Group's specialised register of trials (searched October 5th, 2007) the Cochrane Register of Controlled Trials (The Cochrane Library, Issue 3, 2007), MEDLINE (1966-October 2007), EMBASE (1980 - October 2007) and reference lists of articles.


METHODS
Randomised trials comparing an ovulation suppression agent with placebo or no treatment, or a suppressive agent with danazol or a GnRH with oral contraception in women with endometriosis. A total of twenty three RCTs comparing an ovulation suppression agent with placebo or no treatment, or a suppressive agent with danazol or a GnRH with oral contraception were identified.


METHODS
Two review authors independently extracted data and assessed quality. We contacted study authors for additional information. Quality was assessed by of method of randomization,allocation concealment, blinding, completeness of follow-up, presence or absence of crossover and co-intervention. 2 x 2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using the I(2) test of heterogeneity. Subgroup analysis was conducted on those couples clearly identifiable as infertile or wanting to conceive.


RESULTS
Twenty four trials were included. The odds ratio for pregnancy following ovulation suppression versus placebo or no treatment for all women randomised was 0.79 (95% CI 0.54 to 1.14), P = 0.21 and 0.80 (95% CI 0.51 to 1.24), P = 0.32 respectively for subfertile couples only despite the use of a variety of suppression agents. There was no evidence of benefit from the treatment. The common odds ratio for pregnancy following all agents versus danazol for all women randomised was 1.38 (95% CI 1.05 to 1.82), P = 0.02 and OR 1.37 (95% CI 0.94 to 1.99), P = 0.10 for subfertile couples only. When GnRHa and danazol were directly compared, OR was 1.45 (95% CI 1.08 to 1.95) P = 0.01 for all women randomised and OR 1.63( 95% CI 1.12 to 2.37), P = 0.01 for subfertile couples only in favour of GnRH. No effect was observed for GnRH compared with oral contraception; OR 0.99 (95% CI 0.52 to 1.89), P = 0.98 for all women randomised and OR 0.79 ( 95% CI 0.37 to 1.69), P = 0.55. In all analyses the data were statistically homogeneous (I(2)=0%).


CONCLUSIONS
There is no evidence of benefit in the use of ovulation suppression in subfertile women with endometriosis who wish to conceive.
Hughes
E
E
McMaster University, Department of Obstetrics and Gynaecology, 1200 Main St West, Room HSC-4F7, Hamilton, Ontario, Canada L8N 3Z5. hughese@mcmaster.ca
Brown
J
J
Collins
J J
JJ
Farquhar
C
C
Fedorkow
D M
DM
Vandekerckhove
P
P
D003613:Danazol / Q000627:therapeutic use; D004715:Endometriosis / Q000150:complications* / Q000188:drug therapy; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use*; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy* / Q000209:etiology; D010060:Ovulation / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic
D004965:Estrogen Antagonists; D005300:Fertility Agents, Female; D003613:Danazol