WITHDRAWN: Ovulation induction with urinary follicle stimulating hormone versus human menopausal gonadotropin for clomiphene-resistant polycystic ovary syndrome.
BACKGROUND
The risks of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) are increased in women with clomiphene resistance WHO group 2 dysfunction undergoing ovulation induction as well as the risk of spontaneous abortion if conception takes place. Semi-purified preparations of FSH have been developed in an effort to reduce the impact of exogenous LH, relatively high levels of which are present in human menopausal gonadotropin (hMG). Ovulation induction in women with clomiphene resistant WHO group 2 dysfunction who often have clinical features of polycystic ovarian syndrome (PCOS), is a major challenge. The risks of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) are increased in this population. There also appears to be an increased risk of spontaneous abortion in those who conceive, perhaps associated with elevated LH levels. Semi-purified preparations of FSH have been developed in an effort to reduce the impact of exogenous LH, relatively high levels of which are present in human menopausal gonadotrophins.


OBJECTIVE
To determine the effectiveness of daily FSH versus daily hMG in women with clomiphene-resistant polycystic ovary syndrome (PCOS), in terms of rates of pregnancy and moderate to severe ovarian hyperstimulation syndrome (OHSS).


METHODS
The Cochrane Subfertility Review Group specialised register of controlled trials was searched.


METHODS
All RCTs relevant to the clinical question were selected.


METHODS
A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention.


RESULTS
2x2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using x2.


RESULTS
No significant benefit was demonstrated from semi-purified FSH versus hMG in terms of pregnancy rate: common odds ratio per patient 0.66 (95% CI 0.35-1.24) and per cycle 0.89 (95% CI 0.51-1.53). FSH appeared to be associated with a reduction in moderate to severe OHSS: common odds ratios 0.2 (95% CI 0.09-0.46).


CONCLUSIONS
In women with PCOS, no significant difference could be demonstrated between FSH and hMG, in terms of pregnancy rate. However, given similar cost, potential advantages in terms of purity and a possible reduction in OHSS risk, highly purified or recombinant FSH are likely to be widely adopted in the future. Further research should consider live birth as a primary clinical outcome, given concerns over the association between high androgen and LH levels with spontaneous abortion risk.
Hughes
E
E
McMaster University, Rm HSC-4F7, Dept of Obstetrics & Gynecol, 1200 Main St West, Hamilton, Ontario, Canada, L8N 3Z5. hughese@mcmaster.ca
Collins
J
J
Vandekerckhove
P
P
D002996:Clomiphene / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use*; D005640:Follicle Stimulating Hormone / Q000627:therapeutic use*; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy* / Q000209:etiology*; D008596:Menotropins / Q000627:therapeutic use*; D016471:Ovarian Hyperstimulation Syndrome / Q000209:etiology; D010062:Ovulation Induction / Q000379:methods*; D011085:Polycystic Ovary Syndrome / Q000150:complications* / Q000188:drug therapy; D011247:Pregnancy
D004965:Estrogen Antagonists; D005300:Fertility Agents, Female; D002996:Clomiphene; D008596:Menotropins; D005640:Follicle Stimulating Hormone