Insulin-sensitizing agents as primary therapy for patients with polycystic ovarian syndrome

BACKGROUND: This paper is a systematic review of metformin versus clomiphene citrate (CC) in women with polycystic ovary syndrome (PCOS). METHODS: Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and QUality Of Reporting Of Meta-analyses (QUOROM) guidelines were followed. A systematic computerized literature search was done of seven bibliographic databases. Inclusion criteria included cohort and randomized controlled trials (RCT) of women with PCOS and the following medications: metformin versus placebo; metformin versus CC; metformin plus CC versus placebo plus CC. Rev-man 4.1 and Metaview 4.0 were used to analyse data. Relative risk (RR) estimates were presented. A chi2-test determined the significance of the association. Heterogeneity was determined by the Cochran Q-test. RESULTS: Metformin was 50% better than placebo for ovulation induction in infertile PCOS patients [RR 1.50; 95% confidence interval (CI) 1.13, 1.99]. Metformin was also of benefit in non-infertile (i.e. patients with PCOS who were not complaining of infertility) PCOS patients for cycle regulation compared to placebo (RR 1.45; CI 1.11, 1.90). Metformin was not of confirmed benefit versus placebo for achievement of pregnancy (RR 1.07; CI 0.20, 5.74). Metformin plus CC may be 3-4-fold superior to CC alone for ovulation induction (RR 3.04; CI 1.77, 5.24) and pregnancy (RR 3.65; CI 1.11, 11.99) in women with PCOS. CONCLUSIONS: Metformin is effective for ovulation induction and cycle regulation in this group of patients. Metformin plus CC appears to be very effective for achievement of pregnancy compared to CC alone. No RCTs directly compare metformin to CC but the need for such a trial exists.     

补肾助孕中药对促排卵后子宫内膜LIFmRNA表达的影响

目的探讨补肾助孕中药对多囊卵巢综合征（PCOS）不孕患者促排卵治疗后黄体中期子宫内膜白血病抑制因子（LIF）mRNA表达的影响及意义。方法随机给予患PCOS的不孕妇女两种不同的促排卵方案：克罗米芬（CC）／hCG或CC／hCG加服中药方案。选择促排卵周期中单卵泡成熟排卵的患者为研究对象,其中CC／hCG促排卵者26例,为A组;CC／hCG同时服用补肾助孕中药促排卵者28例,为B组。同期选择25例月经周期正常妇女为对照组,为C组。采用逆转录-聚合酶链反应技术（RT—PCR）对3组妇女黄体中期的子宫内膜LIFmRNA进行半定量分析。结果LIFmRNA在3组妇女着床期子宫内膜均有表达,组间比较有差异（P〈0．05）。B、C组均高于A组（P分别〈0．05、0．01）,差异有显著性;B组和C组间差异无显著性（P〉0．05）。结论单纯CC／hCG促排卵治疗降低了子宫内膜容受性,加服补肾助孕中药后改善了子宫内膜容受性,有利于胚胎着床和临床妊娠率的提高。     

Efficacy of combined metformin-letrozole in comparison with metformin-clomiphene citrate in clomiphene-resistant infertile women with polycystic ovarian disease

BACKGROUND: Adding metformin to clomiphene citrate in clomiphene-resistant polycystic ovary syndrome (PCOS) patients increases ovulatory response. However, because of anti-estrogenic effects of clomiphene it may be associated with lower pregnancy rate, offsetting the ovulation rate benefit. Letrozole is an aromatase inhibitor which induces ovulation without anti-estrogenic effects. METHODS: Infertile women with PCOS were randomly divided into metformin-letrozole (29 patients) and metformin-clomiphene groups (30 patients). After an initial 6-8 weeks of metformin, they received either letrozole (2.5 mg) or clomiphene (100 mg) from day 3-7 of their menstrual cycle. Estradiol (E2) levels, number of follicles, pregnancy rates and endometrial thickness were measured on the day of HCG administration. RESULTS: Mean total E2 and E2 per mature follicle were significantly higher in clomiphene group without a difference in mean number of mature follicles >18 mm and ovulation rate. Endometrial thickness was significantly higher in letrozole group. The pregnancy rate in letrozole group (10 patients, 34.50%) as compared with clomiphene group (5 patients, 16.67%) did not show significant difference, whereas full-term pregnancies were higher in letrozole group [10 patients (34.50%) versus 3 patients (10%)]. CONCLUSION: In clomiphene-resistant PCOS patients, the combination of letrozole and metformin leads to higher full-term pregnancies.     

宫腔内人工授精97个周期临床分析

目的 选择84对患者97个周期的宫腔内人工授精(IUI)进行临床疗效分析。方法 按自然周期、克罗米芬(CC) 补佳乐 HCG、克罗米芬(CC) HMG HCG分为三组进行围排卵期IUI技术比较。结果 84对患者进行97含属期IUI，自然周期11个，有1例妊娠，妊娠率0．09％；克罗米芬(CC) 补佳乐 HCG组57个周期，有8例妊娠，妊娠率14．04％：克罗米芬(CC) HMG HCG组29个周期，有6例妊娠，妊娠率20．69％。结论 使用促排卵药物，尤其克罗米芬(CC) HMG HCG组，诱发排卵数目多，子宫内膜厚。妊娠率高。     

影响夫精宫腔内人工授精临床妊娠率的相关因素分析

目的探讨影响夫精宫腔内人工授精（IUI）临床妊娠率的各种相关因素。方法回顾性分析本生殖中心215例患者进行的488个IUI治疗周期,对女方年龄、不孕年限、不孕病因、IUI周期次数、用药方案、HCG/LH（＋）日成熟卵泡数和内膜厚度、授精时机以及注入宫腔内的前向活动精子数（TMS）和妊娠结局的关系进行分析。结果共获得临床妊娠78例,周期妊娠率16.0%,患者妊娠率36.3%。其中患者年龄的增长、子宫内膜厚度〉14mm、人授时已排卵者妊娠率显著下降;IUI周期次数的增加≥5周期、TMS〈5×106患者的妊娠率也有下降的趋势;男方少弱精子症和子宫内膜异位症患者的妊娠率显著低于宫颈因素和多次促排卵不孕（不明原因？）的患者;患者的不孕年限、用药方案、HCG/LH（＋）日成熟的卵泡数对妊娠结局无显著影响,但卵泡个数为3个的妊娠率有增高的趋势。结论女方年龄、子宫内膜厚度、授精时机及不孕因素是影响IUI结局的重要因素,IUI周期次数、成熟卵泡数、注入宫腔的TMS对妊娠结局也有一定的影响。     

Laparoscopic electrocautery of the ovaries versus recombinant FSH in clomiphene citrate-resistant polycystic ovary syndrome. Impact on women's health-related quality of life

BACKGROUND: Ovulation induction with gonadotrophins is the standard treatment strategy for women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). Laparoscopic electrocautery of the ovaries is an alternative treatment modality, leading to a comparable cumulative pregnancy rate. In deciding which treatment to opt for, women's health-related quality of life (HRQoL) should be taken into account. METHODS: A total of 168 CC-resistant women with PCOS were randomly assigned to receive either the electrocautery strategy, entailing laparoscopic electrocautery of the ovaries followed by CC and recombinant FSH (rFSH) if anovulation persisted, or ovulation induction with rFSH. We assessed women's HRQoL with the standard questionnaires Short Form-36, Rotterdam Symptom Checklist and Center for Epidemiological Studies Depression Scale, administered before randomization and 2, 12 and 24 weeks thereafter. RESULTS: The intention to treat analysis revealed no significant differences between the treatment groups on any of the scales at any point during follow-up. In women without an ongoing pregnancy, those treated with rFSH showed significantly more depressive symptoms than women allocated to the electrocautery strategy, with or without CC, although differences were small. CONCLUSIONS: Overall, HRQoL was not affected in both groups. In women still under treatment, rFSH was slightly more burdensome for women's HRQoL than electrocautery with or without CC.     

不同促排卵方案联合宫腔内人工授精疗效分析

目的比较不同促排卵方案联合宫腔内人工授精（intrauterine insemination,IUI）治疗不孕症的疗效。方法对204例不孕症患者371个周期行IUI治疗,随机分为4组：自然周期（natural cycle,NC）组共102个周期,克罗米酚（Clomiphene,CC）组98个周期,人绝经期促性腺激素（human menopausal gonadotropin,HMG）/人绒毛膜促性腺激素（human chorionic gonadotropin,HCG）（HMG/HCG）组120个周期,CC/HMG/HCG组51个周期,比较不同促排卵方案的治疗效果。结果CC/HMG/HCG组（19.6%）与HMG/HCG组（20.0%）的周期妊娠率显著高于NC组（6.9%）及CC组（8.2%）（P〈0.01）。CC/HIMG/HCG组的HMG用药量和用药天数显著小于HMG/HCG组（P〈0.05）。结论CC/HMG/HCG和HMG/HCG促排卵联合IUI均能提高IUI治疗不孕症的妊娠率,CC/HMG/HCG促排卵药费支出少,更具有优势。     

ASRI2005-93 A new aspect of reproduction in infertility associated with polcystic ovarian syndrome

Introduction:  Polycystic ovarian syndrome (PCOS) is one of the commonest causes of anovulatory infertility presenting with menstrual abnormalities. The common treatment is to ovulate and conceive is Clomiphene citrate but 50% becomes pregnant with first trimester abortion rate high. The aim is for better judgment of efficacy of Clomiphene citrate and recombinant FSH for ovulation induction.
Method:  Patients (120) were divided in two groups: treated with Clomiphene citrate and other on recombinant FSH. Ovarian response was monitored and HCG given to trigger ovulation after appropriate follicular development. The prime out come major cumulative pregnancies after undergoing up to 4 treatment cycles. Results: The study showed that aspects of reproduction with pregnancy rate were more in recombinant FSH as compare to clomiphene citrate. Abortion rate was less in recombinant FSH then clomiphene citrate group. The incidences of OHSS were least in both. The main aspects of reproduction after 4-treatment cycle were 45.8% with recombinant FSH and only 11.2% with Clomiphene citrate.
Conclusions:  Various RCTs have been done before showing benefits of Gonadotrophins over Clomiphene citrate. Study suggests that recombinant FSH effective alternative of Clomiphene citrate in first line treatment for the reproduction of anovulatory PCOS patients.     

补肾活血方影响子宫内膜容受性的实验研究

目的 探讨补肾活血中药对多囊卵巢综合征（PCOS）患者促排卵后子宫内膜容受性的影响。方法 随机给予患PCOS不孕妇女两种不同的促排卵治疗，A组为用克罗米芬（CC）／绒毛膜促性腺激素（HCG）促排卵成功者；B组为用补肾活血方加CC／HCG促排卵成功者。月经周期正常妇女设为C组。用半定量逆转录-聚合酶链反应技术（RT—PCR）检测三组妇女着床期子宫内膜降钙素（CT）mRNA的表达，同日用阴道B超测定子宫内膜厚度，用电化学发光免疫法测血清雌二醇（E2）及孕酮（P）水平。结果 着床期子宫内膜CTmRNA表达比较，A组分别低于B、C组（P分别〈0．05、0.01），B组和C组之间无差异（P〉0．05）。着床期血清E2、P水平及子宫内膜厚度比较，差异无显著性（P〉0．05）。结论 补肾活血方增强了着床期子宫内膜CT的表达，推测中药可改善子宫内膜容受性，有利于胚胎着床和临床妊娠率的提高。     

Uterine effects of clomiphene citrate in women with polycystic ovary syndrome: a prospective controlled study

BACKGROUND: Previous data on the efficacy of clomiphene citrate, the most commonly used drug for treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS), have shown a discrepancy between ovulation and pregnancy rates. In the present subanalysis (of a larger previously published randomized controlled trial), the effect of clomiphene citrate on several ultrasonographic markers of uterine receptivity in PCOS patients who ovulated under treatment was studied. METHODS: Thirty-three PCOS women who ovulated under 150 mg daily clomiphene citrate and 33 healthy controls were studied. Uterine, subendometrial and endometrial blood flows, endometrial thickness and pattern were assessed using serial ultrasonographic assessments. The data were analysed before and after grouping the clomiphene citrate-stimulated ovulatory cycles for reproductive outcome [unfavourable (ovulation alone or early pregnancy loss) or favourable outcome (clinical pregnancy and/or live birth)]. RESULTS: Both before and during treatment, uterine vascularity assessed at all sites was significantly lower in the PCOS group than in controls. Endometrial thickness and pattern were impaired in the PCOS group under clomiphene citrate treatment. A significant difference in all ultrasonographic parameters was observed between cycles ending in unfavourable versus those ended in favourable outcome. CONCLUSIONS: Clomiphene citrate administration alters several surrogate ultrasonographic parameters of uterine receptivity, and this effect could be crucial for its efficacy.     

A controlled study of human chorionic gonadotrophin induced ovulation versus urinary luteinizing hormone surge for timing of intrauterine insemination.

Forty-eight patients in a programme of intrauterine insemination (IUI) were randomized in a cross-over study. All were stimulated with clomiphene citrate (CC) and inseminated either after follicular rupture induced by human chorionic gonadotrophin (HCG) or after a spontaneous urinary luteinizing hormone (LH) surge. The HCG was administered when follicles of 18-22 mm in diameter were observed on ultrasound and IUI was performed 37-40 h thereafter. The monitoring of a urinary LH peak was carried out using a rapid urinary LH test. IUI took place approximately 22 h after detection of the LH surge. Overall, the pregnancy rates were 9.3% (4/43) after HCG induced ovulation and 20.5% (9/44) after spontaneous ovulation (P = 0.12). Analysis of mid-cycle events showed that following sonographic criteria, the HCG injection was performed significantly earlier in the cycle compared with the spontaneous LH surge. In addition, the mean diameter of the preovulatory follicles was significantly smaller and insemination was substantially earlier in the HCG induced cycles. These findings suggest that a beneficial effect arises from allowing the natural process of final follicular maturation to occur.     

GnRH antagonists and mild ovarian stimulation for intrauterine insemination: a randomized study comparing different gonadotrophin dosages

BACKGROUND: The precise role of GnRH antagonists in the armamentarium of drugs for stimulation of ovulation associated with intrauterine insemination remains to be clarified. In this study, we have compared two different protocols employing GnRH antagonists in order to determine the lower effective dose of gonadotrophins to use. METHODS: Sixty-six couples with unexplained infertility or moderate male subfertility were recruited. Starting on day 3 of the cycle, 32 patients were randomized to receive 50 IU of recombinant FSH per day, whereas 34 were treated with 50 IU of recombinant FSH on alternate days. Women received the GnRH antagonist Ganirelix at a dose of 0.25 mg per day starting on the day in which a leading follicle > or =14 mm in mean diameter was visualized, until HCG administration. Insemination was performed 34 h after HCG injection. RESULTS: The regimen with daily recombinant FSH was associated with a lower rate of mono-ovulation (53.3% versus 78.8%, P=0.06) but also with a higher clinical pregnancy rate per initiated cycle (34.4% versus 5.9%, P=0.005). CONCLUSIONS: A protocol of recombinant FSH 50 IU daily and GnRH antagonist may represent an effective and safe regimen for ovulation induction associated with intrauterine insemination.     

The use of metformin as first line treatment in polycystic ovary syndrome

This study evaluated the use of metformin as first line treatment for patients with polycystic ovary syndrome. A retrospective review of patients' files diagnosed with PCOS over 16 months in Department of obstetrics and gynaecology of a Regional hospital. The outcome was the response to metformin treatment regardless of the main complaint. Treatment response was measured by change in LH/FSH ratio, fasting insulin, testosterone, day 21 progesterone and/or pregnancy. A day 21 progesterone greater than 25.5 nmol/l and/or pregnancy were the parameter of ovulation. Thirty-four patients were diagnosed with PCOS. Twenty-five complained of infertility (14 primary and 11 secondary), six patients had oligomenorrhoea or amenorrhoea and three presented with hirsutism. Seventeen patients received metformin as first line treatment. Eight received it with other treatment (5 clomiphene citrate and 3 ant androgens). Nine patients did not receive metformin. This study justifies the use of metformin as an appropriate first line treatment for PCOS.     

Endometrial fluid visualized through ultrasonography during ovarian stimulation in IVF cycles impairs the outcome in tubal factor, but not PCOS, patients

BACKGROUND: The aim of the present study was to examine the impact of the presence of endometrial fluid (seen through ultrasound) on the outcome of IVF cycles and its association with the aetiology of infertility, in tubal and polycystic ovary syndrome (PCOS) cases specifically. METHODS: We retrospectively evaluated the charts of all PCOS and tubal factor infertility patients that underwent IVF between June 1, 2001 and May 31, 2002. Twenty-four PCOS and 14 tubal factor infertility patients in whom endometrial fluid was detected were compared with 94 PCOS and 160 tubal factor patients whose stimulation cycles did not show any fluid collection. The main outcome measures were implantation and pregnancy rates. RESULTS: Implantation rates were lower in the tubal factor patients in the presence of endometrial fluid (6.12% and 21.4%, respectively) in comparison with all other tubal factor infertile patients in whom no fluid accumulation inside the cavity was detected. In PCOS cycles there was no significance in patients with presence of endometrial fluid in comparison with the all other PCOS cycles without any fluid accumulation. CONCLUSIONS: When fluid collection inside the endometrial cavity is first seen during ovarian stimulation of PCOS patients undergoing IVF, embryo transfer can be performed safely if the fluid has disappeared and not returned by the day of embryo transfer. However, in tubal factor cycles one should think of either cancellation of the cycle or cryopreservation of all embryos.     

Predictors for treatment failure after laparoscopic electrocautery of the ovaries in women with clomiphene citrate resistant polycystic ovary syndrome

BACKGROUND: Laparoscopic electrocautery has been put forward as the treatment of choice in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). In order to make an informed treatment decision it would be helpful if we could identify women with PCOS with a high probability of treatment failure following electrocautery of the ovaries. METHODS: Eighty-three women with CC-resistant PCOS were allocated to receive laparoscopic electrocautery followed by CC when anovulation persisted as part of a randomized controlled trial. Multivariable logistic regression analyses using clinical, ultrasonographic and endocrinological parameters were performed to predict (i) failure to ovulate within 8 weeks after electrocautery, and (ii) failure to reach an ongoing pregnancy after electrocautery with or without CC. RESULTS: Of the 83 women, 56 (67%) ovulated within 8 weeks after electrocautery. The model for predicting anovulation after electrocautery included LH/FSH rate, year of menarche and glucose level. Women who were younger at menarche, had a lower LH/FSH ratio and a lower glucose level were more likely to have persistent anovulation. The area under the curve was 0.74. After electrocautery and CC, 41 women reached an ongoing pregnancy. No prognostic parameters could be identified to predict failure to reach an ongoing pregnancy after electrocautery followed by CC. CONCLUSIONS: Persistence of anovulation after electrocautery could be predicted and women with a high risk of persisting anovulation could be distinguished. We were, however, not able to predict treatment failure after electrocautery followed by CC.     

Surrogate end-points or primary outcomes in clinical trials in women with polycystic ovary syndrome?

There are multiple surrogate variables in polycystic ovary syndrome (PCOS), including biometric and biochemical parameters. The number of surrogate variables and their poor validity in relationship to primary clinical end-points pose major problems to conducting a trial in women with PCOS. The aim of this review is to discuss the use of surrogate variables compared with primary clinical end-points in women with PCOS. Arguably the best documented correlation between a surrogate variable and a primary clinical end-point is that between ovulation and pregnancy in women with PCOS. Good correlation has been noted between the increase in ovulation frequency with clomiphene citrate and the chance of pregnancy in women with PCOS. However, ovulation cannot be equated with pregnancy, as a host of other factors may affect the true outcome of interest: a healthy liveborn child. Pregnancy and an improvement in hirsutism are clinical end-points that have been successfully studied in past and ongoing clinical trials in women with PCOS. Many other clinical end-points, such as endometrial cancer and cardiovascular disease, are rare in premenopausal women with PCOS, and may not be suitable as the primary outcome of clinical studies. Future multicentre trials in women with PCOS should focus on primary clinical end-points.     

Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility

BACKGROUND: Adding clomiphene citrate (CC) to FSH for controlled ovarian stimulation (COS) decreases FSH dose required for optimum stimulation. However, because of its anti-estrogenic effects, CC may be associated with lower pregnancy rates offsetting the FSH-dose reduction benefit. Previously, we reported the success of aromatase inhibition in inducing ovulation without antiestrogenic effects. METHODS: A prospective pilot study that included women with unexplained infertility undergoing COS and intrauterine insemination. Thirty-six women received the aromatase inhibitor letrozole + FSH, 18 women received CC + FSH and 56 women received FSH only. Each woman received one treatment regimen in one treatment cycle. All patients were given recombinant or highly purified FSH (50-150 IU/day) starting on day 3 to 7 until day of hCG. RESULTS: The FSH dose needed was significantly lower in letrozole + FSH and CC + FSH groups compared with FSH-only without a difference in number of follicles >1.8 cm. Pregnancy rate was 19.1% in the letrozole + FSH group, 10.5% in the CC + FSH group and 18.7% in the FSH-only group. Both pregnancy rate and endometrial thickness were significantly lower in CC + FSH group compared with the other two groups. Estradiol (E2) levels were significantly lower in the letrozole + FSH group compared with the other two groups. CONCLUSIONS: Similar to CC, aromatase inhibition with letrozole reduces FSH dose required for COS without the undesirable antiestrogenic effects sometimes seen with CC.     

Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis

BACKGROUND: Both selective estrogen receptor modulators, tamoxifen and clomiphene have been used for ovulation induction for patients with anovulatory infertility. This meta-analysis sought to compare the effectiveness of tamoxifen to clomiphene for the induction of ovulation and achievement of pregnancy. METHODS: We searched MEDLINE, BIOSIS, PreMEDLINE, CINAHL, International Pharmaceutical Abstracts, DDSR, ACP Journal Club, DARE and CCTR, along with reference lists and national experts. Inclusion criteria were prospective clinical trials, which compared tamoxifen and clomiphene for ovulation induction in infertile couples with isolated anovulatory infertility. Main outcome measures were ovulation rate and clinical pregnancy rate. Pooled odds ratios were obtained using random effects meta-analysis. RESULTS: Four trials were included. After pooling all the trials, the use of tamoxifen or clomiphene citrate resulted in similar ovulation rates [odds ratio (OR) 0.755, 95% confidence interval (CI) 0.513-1.111]. There was no benefit of tamoxifen over clomiphene citrate in achievement of pregnancy per cycle (OR 1.056, 95% CI 0.583-1.912) or per ovulatory cycle (OR 1.162, 95% CI 0.632-2.134). CONCLUSIONS: Clomiphene citrate and tamoxifen are equally effective in inducing ovulation. Although data regarding pregnancy rates and outcome are limited, there does not appear to be a significant benefit of one medication over the other.     

Low multiple pregnancy rate in combined clomiphene citrate--human menopausal gonadotrophin treatment for ovulation induction or enhancement

Sixty-five infertile women, 37 with anovulation, eight with ovulatory disturbances and 20 with unexplained infertility were treated by a combination of clomiphene citrate (CC) from cycle day 5 (or 3) and human menopausal gonadotrophin (HMG) begun 3 days later for induction or enhancement of ovulation. Monitoring was carried out by measuring preovulatory 17-beta-oestradiol (E2) and progesterone (P) concentrations in blood samples and by follicle measurements using ultrasound. Forty-seven pregnancies resulted with a multiple pregnancy rate of 7.7% for those completed. This incidence is very low and within the range found for CC induction and might result from the later commencement of stimulation compared with many other protocols. These results were achieved with a low incidence of ovarian hyperstimulation syndrome (2.6% per cycle). The HMG doses given were low in comparison with those found in other forms of induction. The deleterious effects of this combined mode of induction on cervical mucus and the occurrence of premature spontaneous ovulation were much less than in the sequential mode of treatment. These results suggest that combined induction treatment by CC and HMG as described offers a means of achieving low rates of multiple pregnancies a known complication in the induction of ovulation.     

Dexamethasone during ovulation induction for in-vitro fertilization: a pilot study

The purpose of the present study was to determine whether adrenalandrogen suppression with dexamethasone (DEX) during ovulationinduction improves the outcome of in-vitro fertilization (IVF)cycles. A total of 25 patients with serum dehydroepiandrosteronesulphate (DHEAS) concentrations>2.5 µg/ml were randomizedto receive either 0.5 mg DEX daily or placebo during ovulationinduction with leuprolide acetate down-regulation plus humanmenopausal gonadotrophins (HMG). Nine patients undergoing asubsequent IVF cycle were crossed over to the other treatmentgroup. Ovarian responsiveness and IVF outcome variables analysedincluded number of follicles>12 mm in diameter, serum oestradiolconcentrations on the day of human chorionic gonadotrophin (HCG)administration, number of ampoules of HMG administered, numberof oocytes retrieved, percentage of oocytes fertilized, numberof embryos transferred, implantation rate and numbers of clinicalpregnancies and live birth pregnancies. The 31 randomized IVFcycles revealed a trend towards a higher implantation rate forthe placebo-treated group compared to the DEX-treated group(24 versus 10%P=0.07). The remainder of the IVF cycle variablesrevealed no statistically significant differences. In conclusion,the suppression of adrenal androgens with DEX in women withDHEAS concentrations >2.5 µg/ml appears to have nobeneficial effects on ovarian responsiveness or clinical orlive birth pregnancy rates.