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Fertility and Sterility Feb 2009To review all available data and recommend a definition for polycystic ovary syndrome (PCOS) based on published peer-reviewed data, whether already in use or not, to... (Review)
Review
OBJECTIVE
To review all available data and recommend a definition for polycystic ovary syndrome (PCOS) based on published peer-reviewed data, whether already in use or not, to guide clinical diagnosis and future research.
DESIGN
Literature review and expert consensus.
SETTING
Professional society.
PATIENTS
None.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
A systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, to identify studies evaluating the epidemiology or phenotypic aspects of PCOS.
RESULT(S)
The Task Force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the Androgen Excess and PCOS (AE-PCOS) Society AE-PCOS Board of Directors. No section was finalized until all members were satisfied with the contents, and minority opinions noted. Statements were not included that were not supported by peer-reviewed evidence.
CONCLUSION(S)
Based on the available data, it is the view of the AE-PCOS Society Task Force that PCOS should be defined by the presence of hyperandrogenism (clinical and/or biochemical), ovarian dysfunction (oligo-anovulation and/or polycystic ovaries), and the exclusion of related disorders. However, a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism, but recognized that more data are required before validating this supposition. Finally, the Task Force recognized and fully expects that the definition of this syndrome will evolve over time to incorporate new research findings.
Topics: Biomarkers; Diagnosis, Differential; Evidence-Based Medicine; Female; Health Status Indicators; Humans; Hyperandrogenism; Menstruation Disturbances; Ovarian Function Tests; Ovary; Ovulation; Phenotype; Polycystic Ovary Syndrome; Predictive Value of Tests; Terminology as Topic
PubMed: 18950759
DOI: 10.1016/j.fertnstert.2008.06.035 -
Clinical Endocrinology Feb 2009To date, no systematic review or meta-analysis has been published of direct head-to-head studies comparing clomiphene citrate (CC) vs. metformin, or the combination of... (Meta-Analysis)
Meta-Analysis Review
Clomiphene citrate, metformin or both as first-step approach in treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS): a systematic review of head-to-head randomized controlled studies and meta-analysis.
BACKGROUND
To date, no systematic review or meta-analysis has been published of direct head-to-head studies comparing clomiphene citrate (CC) vs. metformin, or the combination of both drugs as first-line therapy in anovulatory polycystic ovary syndrome (PCOS) patients seeking pregnancy. The aim of the current paper was to define, if possible, the best evidence-based recommendations regarding the use of CC and/or metformin as the initial treatment of PCOS women with anovulatory infertility.
DESIGN
Systematic review and meta-analysis of the head-to-head randomized controlled trials (RCTs) available in the literature.
METHODS
A bibliographic search was performed using the following bibliographic databases: Medline, EMBASE, Biological Abstracts, Cochrane Controlled Trials Register and Cochrane Database of Systematic Reviews. Reference lists of included studies, other relevant review articles and textbooks were checked for additional citations of interest.
RESULTS
Four head-to-head RCTs were identified and qualified for inclusion in the analysis. No difference in fertility improvement was observed comparing CC with metformin (OR = 1.22, 95% CI 0.23-6.55, P = 0.815), whereas a significant (P < 0.0001) heterogeneity was observed. Homogeneous data showed no difference in fertility improvement between the combination treatment and CC monotherapy (OR = 0.99, 95% CI 0.70-1.40, P = 0.982), but a significant difference in comparison with metformin monotherapy (OR = 0.23, 95% CI 0.14-0.37, P < 0.0001).
CONCLUSIONS
In PCOS patients with anovulatory infertility and not previously treated, the administration of metformin plus CC is not better than monotherapy (metformin alone or CC alone), whereas to date no specific recommendation can be given regarding the use of CC or metformin as first-step drug.
Topics: Anovulation; Clomiphene; Drug Therapy, Combination; Female; Humans; Infertility, Female; Metformin; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic
PubMed: 18691273
DOI: 10.1111/j.1365-2265.2008.03369.x -
The Cochrane Database of Systematic... Jul 2008Anovulation is a common cause for infertility. Drugs used to treat anovulation include selective estrogen receptor modulators, aromatase inhibitors and gonadotrophins.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anovulation is a common cause for infertility. Drugs used to treat anovulation include selective estrogen receptor modulators, aromatase inhibitors and gonadotrophins. Ovulation triggers are used with these drugs, in order to time intercourse. Ovulation triggers without reliable evidence of oocyte maturity could be inappropriately timed, increase costs and psychological stress. This review evaluates different ovulation triggers used when treating anovulatory women with ovulation inducing agents compared to spontaneous ovulation.
OBJECTIVES
To determine the efficacy of administering an ovulation trigger compared to spontaneous ovulation in anovulatory women being treated with ovulation inducing agents.
SEARCH STRATEGY
We searched the Menstrual Disorders and Subfertility Group Trials Register (August week 1 2007), Cochrane Central Register of Controlled Trials (CENTRAL Cochrane library issue 3 2007) and the electronic databases MEDLINE (1950 July week 4 2007), EMBASE(1980 to week 31 2007) and CINAHL (1982 to August week 1 2007) for studies in all languages.
SELECTION CRITERIA
Randomised controlled trials (RCT).
DATA COLLECTION AND ANALYSIS
Two authors independently selected trials, assessed quality and extracted data. Disagreement was resolved by discussion with the third author and by contacting trial authors. Categorical data were analysed using relative risks and their 95% confidence intervals. A random effects model was used in the presence of significant heterogeneity.
MAIN RESULTS
Two RCTs comparing urinary hCG versus no treatment in anovulatory women receiving clomiphene citrate were identified. Urinary hCG did not result in increases in the primary outcome of live birth rate over no treatment { OR 0.98, 95% CI 0.52 to 1.83}.Among the secondary outcomes, urinary hCG did not increase ovulation rate ( OR 0.95, 95% CI 0.49 to 1.83), clinical pregnancy rate (OR 1.02, 95% CI 0.56 to 1.88), multiple pregnancy rate (OR 0.47, 95% CI 0.05 to 4.59), miscarriage rate( OR 1.18, 95% CI 0.18 to 7.66) and preterm delivery (OR 0.12,95% CI 0.00 to 6.29) compared to no treatment. Trials evaluating other ovulation triggers were not identified.
AUTHORS' CONCLUSIONS
There is inadequate evidence to recommend or refute the use of urinary hCG, as an ovulation trigger, in anovulatory women being treated with clomiphene citrate. We did not find trials evaluating the use of ovulation triggers in anovulatory women, being treated with other ovulation inducing agents.
Topics: Anovulation; Chorionic Gonadotropin; Clomiphene; Female; Fertility Agents, Female; Humans; Ovulation Induction; Pregnancy; Randomized Controlled Trials as Topic; Reproductive Control Agents
PubMed: 18646175
DOI: 10.1002/14651858.CD006900.pub2 -
The Cochrane Database of Systematic... Oct 2007Dysfunctional uterine bleeding (DUB) is excessively heavy, prolonged or frequent bleeding of uterine origin which is not due to pregnancy or to recognisable pelvic or... (Review)
Review
BACKGROUND
Dysfunctional uterine bleeding (DUB) is excessively heavy, prolonged or frequent bleeding of uterine origin which is not due to pregnancy or to recognisable pelvic or systemic disease. Anovulation may be inferred from a number of observations but, in the normal clinical situation, anovulation is often assumed when a woman presents with heavy, prolonged or frequent bleeding, particularly in those who are at the extremes of reproductive life and in women known to have polycystic ovarian syndrome. Menstrual bleeding that is irregular or excessive is poorly tolerated by the majority of women. Changes in the length of the menstrual cycle generally imply disturbances of the hypothalamo-pituitary-ovarian (HPO) axis. In anovulatory DUB with acyclic (irregular) oestrogen production there will be no progesterone withdrawal from oestrogen primed endometrium and so cycles are irregular. Prolonged oestrogen stimulation may cause a build up of endometrium with erratic bleeding as it breaks down and is expelled. This is the rationale for using cyclical progestogens during the second half of the menstrual cycle, in order to provoke a regular withdrawal bleed. Continuous progestogen is intended to induce endometrial atrophy and hence to prevent oestrogen-stimulated endometrial proliferation. Progestogens, and oestrogens and progestogens in combination are already widely used in the management of irregular or excessive bleeding due to DUB but the regime, dose and type of progestogen used varies widely, with little consensus about the optimum treatment approach.
OBJECTIVES
To determine the effectiveness and acceptability of progestogens alone and oestrogens and progestogens in combination in the management of irregular bleeding associated with anovulation.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched 4 May 2007), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to May 2007), EMBASE (1985 to May 2007), CINAHL (1982 to May 2007), Biological Abstracts (1969 to May 2007), Current Contents (1980 to 2007) and reference lists of articles.
SELECTION CRITERIA
All randomised controlled trials of progestogens (via any route) alone or in combination with oestrogens in the treatment of irregular bleeding associated with anovulation.
DATA COLLECTION AND ANALYSIS
Study quality assessment and data extraction were carried out independently by two review authors. Both authors were experts in the content matter.
MAIN RESULTS
No randomised trials were identified which compared progestogens with oestrogens and progestogens or with placebo in the management of irregular bleeding associated with anovulation. Only one small, non-randomised study compared two progestogen regimes in the management of heavy and irregular bleeding in women with confirmed anovulation. One randomised study compared the effects of two progestogens on endometrial histology in women with a variety of menstrual symptoms, half of whom had cystic glandular hyperplasia.
AUTHORS' CONCLUSIONS
There is a paucity of randomised studies relating to the use of progestogens and of oestrogens and progestogens in combination in the treatment of irregular bleeding associated with anovulation. Further research is needed to establish the role of these treatments in the management of this common gynaecological problem.
Topics: Adult; Anovulation; Drug Therapy, Combination; Estrogens; Female; Humans; Menorrhagia; Progestins
PubMed: 17943761
DOI: 10.1002/14651858.CD001895.pub2 -
The Cochrane Database of Systematic... Jul 2007Surgical ovarian wedge resection was the first established treatment for women with anovulatory polycystic ovary syndrome (PCOS) but was largely abandoned due to the... (Review)
Review
BACKGROUND
Surgical ovarian wedge resection was the first established treatment for women with anovulatory polycystic ovary syndrome (PCOS) but was largely abandoned due to the risk of postsurgical adhesions and the introduction of medical ovulation induction with clomiphene and gonadotrophins. However, women with PCOS who are treated with gonadotrophins often have an over-production of follicles which may result in ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. Moreover, gonadotrophins, though effective, are costly and time-consuming requiring intensive monitoring. Surgical therapy with laparoscopic ovarian 'drilling' (LOD) may avoid or reduce the need for gonadotrophins or may facilitate their usefulness. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions than with traditional surgical approaches. Many uncontrolled observational studies have claimed that ovarian drilling is followed, at least temporarily, by a high rate of spontaneous ovulation and conception or that subsequent medical ovulation induction becomes easier.
OBJECTIVES
To determine the effectiveness and safety of laparoscopic ovarian drilling compared with ovulation induction for subfertile women with clomiphene-resistant PCOS.
SEARCH STRATEGY
We used the search strategy of the Menstrual Disorders and Subfertility Group.
SELECTION CRITERIA
We included randomised controlled trials of subfertile women with clomiphene-resistant PCOS who undertook laparoscopic ovarian drilling in order to induce ovulation.
DATA COLLECTION AND ANALYSIS
Sixteen trials were identified and nine were included in the review. All trials were assessed for quality criteria. The primary outcomes were live birth, ovulation and pregnancy rates and the secondary outcomes were rates of miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome and cost.
MAIN RESULTS
There was no evidence of a difference in live birth or clinical pregnancy rate between LOD and gonadotrophins and the pooled odds ratios (OR) (all studies) were 1.04 (95% CI 0.59 to 1.85) and 1.08 (95% CI 0.69 to 1.71) respectively. Multiple pregnancy rates were lower with ovarian drilling than with gonadotrophins (1% versus 16%; OR 0.13, 95% CI 0.03 to 0.52). There was no evidence of a difference in miscarriage rates between the two groups (OR 0.81, 95% 0.36 to 1.86).
AUTHORS' CONCLUSIONS
There was no evidence of a difference in the live birth rate and miscarriage rate in women with clomiphene-resistant PCOS undergoing LOD compared to gonadotrophin treatment. The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive. However, there are ongoing concerns about long-term effects of LOD on ovarian function.
Topics: Anovulation; Diathermy; Female; Humans; Infertility, Female; Laparoscopy; Laser Therapy; Ovulation Induction; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic
PubMed: 17636653
DOI: 10.1002/14651858.CD001122.pub3 -
The Journal of Clinical Endocrinology... Mar 2006For the last 40 yr, the first line of treatment for anovulation in infertile women has been clomiphene citrate (CC). CC is a safe, effective oral agent but is known to... (Review)
Review
CONTEXT
For the last 40 yr, the first line of treatment for anovulation in infertile women has been clomiphene citrate (CC). CC is a safe, effective oral agent but is known to have relatively common antiestrogenic endometrial and cervical mucous side effects that could prevent pregnancy in the face of successful ovulation. In addition, there is a significant risk of multiple pregnancy with CC, compared with natural cycles. Because of these problems, we proposed the concept of aromatase inhibition as a new method of ovulation induction that could avoid many of the adverse effects of CC. The objective of this review was to describe the different physiological mechanisms of action for CC and aromatase inhibitors (AIs) and compare studies of efficacy for both agents for ovulation induction.
EVIDENCE ACQUISITION
We conducted a systematic review of all the published studies, both controlled and noncontrolled, comparing CC and AI treatment, either alone or in combination with gonadotropins, for ovulation induction or augmentation, identified through the Entrez-PubMed search engine.
EVIDENCE SYNTHESIS
Because of the recent acceptance of the concept of using AIs for ovulation induction, few controlled studies were identified, and the rest of the studies were pilot or preliminary comparisons. Based on these studies, it appears that AIs are as effective as CC in inducing ovulation, are devoid of any antiestrogenic side effects, result in lower serum estrogen concentrations, and are associated with good pregnancy rates with a lower incidence of multiple pregnancy than CC. When combined with gonadotropins for assisted reproductive technologies, AIs reduce the dose of FSH required for optimal follicle recruitment and improve the response to FSH in poor responders.
CONCLUSIONS
Preliminary evidence suggests that AIs may replace CC in the future because of similar efficacy with a reduced side effect profile. Although worldwide experience with AIs for ovulation induction is increasing, at present, definitive studies in the form of randomized controlled trials comparing CC with AIs are lacking.
Topics: Anovulation; Aromatase Inhibitors; Clomiphene; Female; Humans; Ovulation; Ovulation Induction
PubMed: 16384846
DOI: 10.1210/jc.2005-1923 -
The Cochrane Database of Systematic... Jul 2005Problems in inducing ovulation in women with polycystic ovary syndrome (PCOS) and anovulation (failure to ovulate) are well recognised. Surgical ovarian wedge resection... (Review)
Review
BACKGROUND
Problems in inducing ovulation in women with polycystic ovary syndrome (PCOS) and anovulation (failure to ovulate) are well recognised. Surgical ovarian wedge resection was the first established treatment for anovulatory PCOS patients but was largely abandoned due to the risk of post-surgical adhesions and the introduction of medical ovulation induction with clomiphene and gonadotrophins. However patients with PCOS treated with gonadotrophins often have an over-production of follicles and are exposed to the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. Moreover ovulation induction with gonadotrophins, though effective, is an expensive, inconvenient and time-consuming treatment requiring intensive monitoring. Surgical therapy with laparoscopic ovarian "drilling" (LOD) may avoid or reduce the need for gonadotrophins or may facilitate their use. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions. Many uncontrolled observational studies have claimed that ovarian drilling is followed, at least temporarily, by a high rate of spontaneous ovulation and conception, and/or that subsequent medical ovulation induction becomes easier.
OBJECTIVES
To determine the effectiveness and safety of laparoscopic ovarian drilling compared with ovulation induction for subfertile women with clomiphene-resistant PCOS.
SEARCH STRATEGY
We used the search strategy of the Menstrual Disorders and Subfertility Group.
SELECTION CRITERIA
We included randomised controlled trials of subfertile women with clomiphene-resistant PCOS that undertook laparoscopic ovarian drilling in order to induce ovulation.
DATA COLLECTION AND ANALYSIS
Fifteen trials were identified and six were included in the review. All trials were assessed for quality criteria. The primary outcomes were live birth, ovulation and pregnancy rates and the secondary outcomes were rates of miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome and cost.
MAIN RESULTS
There was no evidence of a difference in live births or ongoing pregnancies between LOD and gonadotrophins and the pooled Odds Ratio (OR) (all studies) was 1.04 (95% CI 0.74, 1.99) and 1.16 (95% CI 0.72, 1.86) respectively. Multiple pregnancy rates were lower with ovarian drilling than with gonadotrophins (1% vs 16%, OR: 0.13, 95% CI: 0.03 to 0.59). There was no evidence of a difference in miscarriage rates between the two groups (OR 0.81, 955% 0.36, 1.86).
AUTHORS' CONCLUSIONS
There was no evidence of a difference in the live birth rate and miscarriage rate in women with clomiphene resistant PCOS undergoing LOD compared to gonadotrophin treatment. The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive. However, there are ongoing concerns about long term effects of LOD on ovarian function.
Topics: Anovulation; Diathermy; Female; Humans; Infertility, Female; Laparoscopy; Laser Therapy; Ovulation Induction; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic
PubMed: 16034856
DOI: 10.1002/14651858.CD001122.pub2 -
The Cochrane Database of Systematic... Jan 2005Infertility due to anovulation is a common problem in women. The first line oral treatment is with anti-oestrogens, such as clomiphene citrate. Unfortunately there may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infertility due to anovulation is a common problem in women. The first line oral treatment is with anti-oestrogens, such as clomiphene citrate. Unfortunately there may be resistance and alternative and adjunctive treatments have been developed. These include tamoxifen, dexamethasone, bromocriptine and aromatase inhibitors (AIs).
OBJECTIVES
To determine the relative effectiveness of anti-oestrogen agents, with or without medical adjuncts, in women with WHO group 2 anovulation.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Subfertility Group trial register (searched 5th July 2004), CENTRAL (The Cochrane Library Issue 2 2004), MEDLINE (1966 to June 2004) and EMBASE (1980 to June 2004) for identification of relevant randomised controlled trials (RCTs). Additionally the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs were searched.
SELECTION CRITERIA
RCTs that compare oral anti-oestrogen agents for ovulation induction (alone or in conjunction with medical adjuncts) in anovulatory subfertility, were considered for inclusion in the review. Metformin and other insulin sensitizing agents were not included. Hyperprolactinaemic infertility was not included.
DATA COLLECTION AND ANALYSIS
Data extraction and quality assessment was done independently by two reviewers. The primary outcome was live birth, secondary outcomes were: pregnancy, ovulation, miscarriage, multiple pregnancy, overstimulation, ovarian hyperstimulation syndrome and patient reported adverse effects.
MAIN RESULTS
Twelve RCTs were found and included in this review. No trials reported live birth as an outcome. Miscarriage and multiple pregnancy rates were poorly reported. Clomiphene was shown to be effective in increasing pregnancy rate when compared to placebo (fixed OR 5.8, 95% CI 1.6 to 21.5; NNT 5.9, 95% CI 3.6 to 16.7). No evidence of a difference in effect was found between clomiphene and tamoxifen (fixed OR 1.0, 95% CI 0.5 to 2.1). The use of clomiphene in combination with tamoxifen did not find any evidence of effect on pregnancy rate when compared to clomiphene alone (fixed OR 3.3, 95% CI 0.1 to 91.6). The comparison between two AIs (letrozole and anastrozole) did not find any evidence of a difference in effect on pregnancy rate (fixed OR 1.9, 95% CI 0.4 to 8.9). For the intervention of clomiphene plus ketoconazole vs clomiphene no evidence of a difference in effect for pregnancy rate was found (fixed OR 2.4, 95% CI 0.9 to 6.4). For clomiphene plus bromocriptine vs clomiphene no evidence of a difference in effect on pregnancy rate was found (fixed OR 1.0, 95% CI 0.3 to 3.0) rates. However, clomiphene plus dexamethasone treatment resulted in a significant improvement in the pregnancy rate (fixed OR 11.3, 95% CI 5.3 to 24.0; NNT 2.7, 95% CI 2.1 to 3.6) when compared to clomiphene alone as did clomiphene plus pretreatment with combined oral contraceptives (fixed OR 27.2, 95% CI 3.1 to 235.0; NNT 2.0, 95% CI 1.4 to 3.4).
AUTHORS' CONCLUSIONS
This review shows evidence supporting the effectiveness of the current first line treatment, clomiphene citrate. No evidence of a difference in effect was found between clomiphene and tamoxifen. The use of dexamethasone as an adjunct to clomiphene therapy appears promising as do combined oral contraceptives. This review has highlighted a gap in the literature on effects of these drugs on outcomes such as miscarriage rate. Evidence in favour of these interventions is flawed. RCTs of adequate power and of high methodological quality are required for the older treatments such as clomiphene, alone and with medical adjuncts, and also for the newer drugs such as the AIs.
Topics: Anovulation; Contraceptives, Oral, Combined; Estrogen Antagonists; Female; Humans; Infertility, Female; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic
PubMed: 15674894
DOI: 10.1002/14651858.CD002249.pub3 -
Current Opinion in Obstetrics &... Dec 2004Metformin has become an established treatment for women with polycystic ovary syndrome, although controversy remains as to how effective it is and in which populations... (Review)
Review
PURPOSE OF REVIEW
Metformin has become an established treatment for women with polycystic ovary syndrome, although controversy remains as to how effective it is and in which populations it should be used. This review examines the recent literature in order to ascertain the evidence for the benefits and disadvantages of using metformin in women with polycystic ovary syndrome.
RECENT FINDINGS
A Cochrane systematic review and metaanalysis examined the evidence for metformin in treating polycystic ovary syndrome. Since this was published there have been a number of new trials, some of which have been reasonably large involving participants from many different countries.
SUMMARY
Evidence shows that metformin is effective in inducing ovulation, has some marginal benefit in improving aspects of the metabolic syndrome, improves objective measures of hirsutism, and seems to be effective in both obese and lean individuals. However, it has significant side effects, and the high levels of effectiveness that were reported by some early trials have not been replicated. Metformin should always be used as an adjuvant to general lifestyle improvements, and not as a replacement for increased exercise and improved diet.
Topics: Anovulation; Body Weight; Clomiphene; Drug Therapy, Combination; Female; Fertility Agents, Female; Glucose Metabolism Disorders; Gonadotropins; Humans; Hypoglycemic Agents; Metformin; Polycystic Ovary Syndrome
PubMed: 15534444
DOI: 10.1097/00001703-200412000-00008 -
Human Reproduction Update 2003A systematic review was conducted to determine whether initial screening characteristics of women with normogonadotrophic anovulatory infertility predict clinically... (Meta-Analysis)
Meta-Analysis
A systematic review was conducted to determine whether initial screening characteristics of women with normogonadotrophic anovulatory infertility predict clinically significant outcomes of ovulation induction with gonadotrophins, and to obtain pooled estimates of their predictive value through meta-analysis. Only those studies in which pre-treatment screening characteristics (such as body mass index, serum LH and androgens, insulin sensitivity and ultrasound appearance of ovaries) were related to outcome parameters (such as total amount of FSH administered, cancellation, ovulation, pregnancy and miscarriage), were included in this analysis. Thirteen studies fulfilled the inclusion criteria. A positive association was seen in all studies between the level of obesity (definition applied as assessed by individual studies) and total amount of FSH administered [weighted mean difference (WMD) of 771 IU (95% confidence interval (CI): 700-842)]. Pooled odds ratios (OR) of 1.86 (95% CI: 1.13-3.06) and 0.44 (95% CI: 0.31-0.61) were found between obesity with cancellation and ovulation respectively. Pooled analysis did not show a significant association between obesity and pregnancy rate. The pooled OR for obese versus non-obese women and miscarriage rate was significant [3.05 (95% CI: 1.45-6.44)]. Association measures between insulin resistance (definition applied as assessed by individual studies) and total amount of FSH administered produced a WMD of 351 (95% CI: 73-630) IU. A pooled OR of 0.29 (95% CI: 0.10-0.80) was found for insulin resistance with pregnancy rate. The pooled OR for insulin resistance (hyperinsuliaemia versus normoinsuliaemia) and miscarriage rate was not significant. A pooled OR of 1.04 (95% CI: 1.01-1.07) was found for LH (IU/l) with pregnancy rate. The pooled OR for LH and miscarriage rate was not significant. Finally, pooled analysis did not find a significant association between testosterone and pregnancy rate. In conclusion, the best available evidence, though limited, suggests that the most clinically useful predictors of gonadotrophin ovulation induction outcome in normogonadotrophic women are obesity and insulin resistance.
Topics: Abortion, Spontaneous; Anovulation; Female; Follicle Stimulating Hormone; Gonadotropins; Humans; Infertility, Female; Insulin Resistance; Obesity; Ovulation Induction; Pregnancy; Reference Values; Treatment Outcome
PubMed: 14640376
DOI: 10.1093/humupd/dmg035