WITHDRAWN: Gonadotrophin-releasing hormone analogues for pain associated with endometriosis.

BACKGROUND: Endometriosis is a common gynaecological condition that frequently presents with the symptom of pain. The precise pathogenesis (mode of development) of endometriosis is unclear but it is evident that endometriosis arises by the dissemination of endometrium to ectopic sites and the subsequent establishment of deposits of ectopic endometrium. The observation that endometriosis is rarely seen in the hypo-oestrogenic (low levels of oestrogen) post-menopausal woman led to the concept of medical treatment by induction of a pseudo-menopause using Gonadotrophin Releasing Hormone Analogues (GnRHas). When administered in a non-pulsatile manner (the pituitary is normally stimulated by pulses of natural GnRH and all analogues act on the pituitary at a constant level) their use results in down regulation (switching off) of the pituitary and a hypogonadotrophic hypogonadal state (low levels of female hormones due to non stimulation of the ovary). OBJECTIVES: To determine the effectiveness of Gonadotrophin Releasing Hormone analogues (GnRHas) in the treatment of the painful symptoms of endometriosis by comparing them with no treatment, placebo, other recognised medical treatments, and surgical interventions. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility review group (please see Review Group details) was used to identify all randomised trials of the use of GnRHas for the treatment of the painful symptoms of endometriosis. SELECTION CRITERIA: Trials were included if they were randomised, and considered the effectiveness of GnRHas in the treatment of the painful symptoms of endometriosis. DATA COLLECTION AND ANALYSIS: Twenty-six studies had data appropriate for inclusion in the review. The largest group (15 studies) compared GnRHas with danazol. There are five studies comparing GnRHas with GnRHas plus add-back therapy, three comparing GnRHa with GnRHa in a different form or dose, one compares them with gestrinone, one with the combined oral contraceptive pill, and one with placebo. Data was extracted independently by two reviewers. The authors of eleven studies have been contacted to clarify missing or unclear data. Only four have replied to date. Data on relief of pain, change in revised American Fertility Society (rAFS) scores, and side effects was collected. MAIN RESULTS: No difference was found between GnRHas and any of the other active comparators with respect to pain relief or reduction in endometriotic deposits. The side effect profiles of the different treatments were different, with danazol and gestrinone having more androgenic side effects, while GnRHas tend to produce more hypo-oestrogenic symptoms. AUTHORS' CONCLUSIONS: There is little or no difference in the effectiveness of GnRHas in comparison with other medical treatments for endometriosis. GnRHas do appear to be an effective treatment. Differences that do exist relate to side effect profiles. Side effects of GnRHas can be ameliorated by the addition of addback therapy.

Progestagens and anti-progestagens for pain associated with endometriosis.

BACKGROUND: Endometriosis is a gynaecological condition that presents either with the problem of infertility or with painful symptoms. The clinical observation of an apparent resolution of symptoms during pregnancy gave rise to the concept of treating patients with a pseudo-pregnancy regime. Initially combinations of high dose oestrogens and progestagens were used but this was subsequently replaced by progestogens alone. More recently progestogens of both progestagens and anti-progestagens in the treatment of symptomatiprogestogenssis OBJECTIVES: To determine the effectiveness of both the progestagens and anti-progestagens in the treatment of painful symptoms ascribed to the diagnosis of endometriosis. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility Group was utilised to identify all publications which described or might have described randomised trials of any progestagen or any anti-progestagen in the treatment of symptomatic endometriosis. SELECTION CRITERIA: Trials were included if they were randomised and considered the effectiveness of either a progestagen or an anti-progestagen in the treatment of painful symptoms associated with endometriosis. DATA COLLECTION AND ANALYSIS: Seven studies were considered to be appropriate for inclusion in this review. Only three studies evaluating progestagens were included (comparison with placebo, danazol and oral contraceptive plus danazol). All other studies compared the anti-progestagen, gestrinone, with other medical therapies. MAIN RESULTS: Progestagens appear to be an effective therapy for the painful symptoms associated with endometriosis. Gestrinone is as effective as other established medical therapies (danazol and GnRH analogues). REVIEWER'S CONCLUSIONS: The limited available data suggests that both continuous progestagens and anti-progestagens are effective therapies in the treatment of painful symptoms associated with endometriosis. Progestagens given in the luteal phase are not effective. These conclusions should be accepted cautiously due to a lack of data.

Gonadotrophin-releasing hormone analogues for pain associated with endometriosis.

BACKGROUND: Endometriosis is a common gynaecological condition that frequently presents with the symptom of pain. The precise pathogenesis (mode of development) of endometriosis is unclear but it is evident that endometriosis arises by the dissemination of endometrium to ectopic sites and the subsequent establishment of deposits of ectopic endometrium. The observation that endometriosis is rarely seen in the hypo-oestrogenic (low levels of oestrogen) post-menopausal woman led to the concept of medical treatment by induction of a pseudo-menopause using Gonadotrophin Releasing Hormone Analogues (GnRHas). When administered in a non-pulsatile manner (the pituitary is normally stimulated by pulses of natural GnRH and all analogues act on the pituitary at a constant level) their use results in down regulation (switching off) of the pituitary and a hypogonadotrophic hypogonadal state (low levels of female hormones due to non stimulation of the ovary). OBJECTIVES: To determine the effectiveness of Gonadotrophin Releasing Hormone analogues (GnRHas) in the treatment of the painful symptoms of endometriosis by comparing them with no treatment, placebo, other recognised medical treatments, and surgical interventions. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility review group (please see Review Group details) was used to identify all randomised trials of the use of GnRHas for the treatment of the painful symptoms of endometriosis. SELECTION CRITERIA: Trials were included if they were randomised, and considered the effectiveness of GnRHas in the treatment of the painful symptoms of endometriosis. DATA COLLECTION AND ANALYSIS: Twenty-six studies had data appropriate for inclusion in the review. The largest group (15 studies) compared GnRHas with danazol. There are 5 studies comparing GnRHas with GnRHas plus add-back therapy, 3 comparing GnRHa with GnRHa in a different form or dose, one compares them with gestrinone, one with the combined oral contraceptive pill, and one with placebo. Data was extracted independently by two reviewers. The authors of 11 studies have been contacted to clarify missing or unclear data. Only 4 have replied to date. Data on relief of pain, change in revised American Fertility Society (rAFS) scores, and side effects was collected. MAIN RESULTS: No difference was found between GnRHas and any of the other active comparators with respect to pain relief or reduction in endometriotic deposits. The side effect profiles of the different treatments were different, with danazol and gestrinone having more androgenic side effects, while GnRHas tend to produce more hypo-oestrogenic symptoms. REVIEWER'S CONCLUSIONS: There is little or no difference in the effectiveness of GnRHas in comparison with other medical treatments for endometriosis. GnRHas do appear to be an effective treatment. Differences that do exist relate to side effect profiles. Side effects of GnRHas can be ameliorated by the addition of addback therapy.

Single versus double insemination: a retrospective audit of pregnancy rates with two treatment protocols in donor insemination.

Our objective was to evaluate the effect of a change in treatment protocols, suggested following an inspection visit by the regulatory authority, from single to double inseminations during donor insemination treatment cycles. We therefore conducted a retrospective audit of pregnancy rates in the reproductive medicine clinic of a major teaching hospital. All patients were treated for male factor infertility by donor insemination, without ovulation induction with gonadotrophins between October 1992 and December 1995. The main outcome measures were cumulative conception and live birth rates. During the study period 250 patients underwent treatment and 650 single insemination and 277 double insemination treatment cycles were undertaken. The pregnancy rate per cycle was 0.054 and 0.119 for single and double insemination respectively. After six cycles the cumulative pregnancy rates were 0.28 and 0.47 and the take-home baby rates were 0.25 and 0.37 for single and double inseminations respectively. The change in practice from single to double insemination resulted in a doubling of the pregnancy rate per treatment cycle. Cumulative pregnancy rates after two treatment cycles of double insemination were comparable with those achieved after six cycles of single insemination. These results have significant implications for both patients and purchasers.