Clomiphene citrate versus tamoxifen for ovulation induction in women with PCOS: a prospective randomized trial

Objective

To reevaluate the efficacy of induction of ovulation with CC versus TMX in a group of anovulatory subfertile women with PCOS in a randomized controlled trial.

Study design

A prospective randomized controlled study in which 371 PCOS patients were randomly allocated into two treatment groups: group A (187 patients) where women received CC and group B (184 patients) where they received Tamoxifen for one treatment cycle. The outcome measures were number of growing and mature follicles, serum E₂ (pg/ml), serum progesterone (ng/ml) and endometrial thickness, the occurrence of pregnancy and miscarriage.

Results

The number of stimulated follicles reaching ≥16 mm diameter was significantly more in the CC group compared to Tamoxifen stimulated group (2.1 SD ± 0.1 vs. 1.1 SD ± 0.7, p < 0.0001). The endometrium at the time of hCG administration was significantly thicker in the TMX group (10.1 ± 0.1 mm vs. 9.3 ± 0.4 mm, p < 0.0001). Ovulation occurred in 120/187 cycles (64%) in the CC group and 95/184 cycles (51.6%) in the TMX group with a significant difference between two groups in favors of clomiphene (p = 0.01). Serum E₂, on the day of hCG administration, was significantly higher in the clomiphene group (p < 0.0001). Pregnancy occurred in 35/187 cycles in group A (18.7%) and 20/184 cycles (10.8%) in group B and the difference was statistically significant (p = 0.04).

Conclusions

Clomiphene citrate is more successful than tamoxifen as a first line therapy for ovulation induction in women with PCOS.     

Combined metformin and clomiphene citrate versus highly purified FSH for ovulation induction in clomiphene-resistant PCOS women: a randomised controlled trial

Aim.?To compare the effect of combined metformin–clomiphene citrate (CC) with highly purified urinary FSH (HP-uFSH) for ovulation induction in CC-resistant women with polycystic ovary syndrome (PCOS).

Methods.?One-hundred fifty-three anovulatory women with CC-resistant PCOS were selected in this randomised controlled trial. Patients received combined metformin–CC (n?=?75, 205 cycles) or HP-uFSH (n?=?78, 186 cycles) for three cycles. Outcome measures were; Ovulation rate, number of growing and mature follicles, serum E2, serum P, endometrial thickness, pregnancy and miscarriage rates.

Results.?The ovulation rate per cycle was significantly higher in the HP-uFSH group (83.8% vs. 62%, p?=?0.01). The number of follicles ≥12?mm ≥14?mm and ≥18?mm on the hCG day was significantly greater in the HP-uFSH group (p?=?0.01, p?=?0.02 and p?=?0.03, respectively). Pregnancy occurred in 23/205 cycles (11.2%) in combined metformin–CC group and 40/186 cycles (21.5%) in the HP-uFSH group; the difference was statistically significant (p?=?0.02). Two patients in the HP-uFSH group suffered mild OHSS.

Conclusions.?Combined metformin–CC resulted in modest ovulation and pregnancy rates without side effects. It is logical to offer this first for CC-resistant PCOS women before resorting to more expensive alternatives especially in developing communities where economic aspects of therapy are important.     

Clomiphene citrate plus cabergoline versus clomiphene citrate for induction of ovulation in infertile euprolactinemic patients with polycystic ovary syndrome: A randomized clinical trial

Objective

To compare the effect of adjunctive use of cabergoline with clomiphene citrate (CC) in infertile polycystic ovarian syndrome (PCOS) patients with normal prolactin level.

Comparison of letrozole with continuous gonadotropins and clomiphene-gonadotropin combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure: a randomized prospective clinical trial

Purpose  Letrozole, though reported to be an effective ovulation inducing agent, warrants larger randomized trials. The purpose of this study is to compare the efficacy of letrozole with that of rFSH and clomiphene citrate(CC)/rFSH for ovarian stimulation in IUI cycles. Methods  Randomized, prospective, single-blinded clinical trial. 1387 PCOS women after CC failure were randomized into three groups: Group A received letrozole, Group B received CC with two doses rFSH and Group C received continuous rFSH day 2 onwards until hCG injection. Results  Group A, B and C had an ovulation rate of 79.30%, 56.95% and 89.89% and cycle cancellation rate of 20.70%, 43.05% and 10.11%, respectively. Pregnancy rates in Group A, B and C were 23.39%, 14.35% and 17.92%, while the miscarriage rates were 13.80%, 16.67% and 14.52%, respectively. Conclusion  Letrozole appears to be a suitable ovulation inducing agent in PCOS women with CC failure and is found to be most effective when baseline estradiol level >60 pg/ml. Capsule Letrozole appears to be an effective ovulation inducing agent as compared to clomiphene-rFSH and continuous rFSH protocols in PCOS women after clomiphene citrate failure.     

A randomized controlled trial comparing low dose vaginal misoprostol and dinoprostone gel for labor induction

Objectives

To compare the safety and efficacy of low dose misoprostol and dinoprostone for cervical ripening and labor induction

Methods

It was an open label randomized controlled trial conducted at department of Obstetrics & Gynecology, Dr TMA Pai Rotary Hospital, Karkala. The main outcome measure was induction-to-vaginal delivery interval. Secondary outcome measures were the labor characteristics, maternal complications and neonatal outcomes.

Results

Out of 320 eligible women included for final analysis, 159 received misoprostol and 161 dinoprostone. There was no significant difference between the two groups in induction-to-vaginal delivery interval, mode of delivery, number of women delivering within 24 hours and neonatal outcomes. The efficacies of the two prostaglandins were similar.

Conclusion

Low dose misoprostol is as efficient as dinoprostone in achieving active labor and delivering with in 24 hours. The maternal and neonatal outcomes associated with each group were similar. It is a cheaper alternative for labor induction.     

A randomized controlled trial of laparoscopic ovarian diathermy versus gonadotropin therapy for women with clomiphene citrate-resistant polycystic ovary syndrome

OBJECTIVE: To compare the effectiveness of laparoscopic ovarian diathermy with gonadotropin ovulation induction for women with clomiphene citrate-resistant polycystic ovary syndrome. DESIGN: Randomized controlled trial. SETTING: A tertiary referral fertility clinic. PATIENT(S): Women with anovulatory infertility secondary to clomiphene-resistant polycystic ovary syndrome. Inclusion criteria were age of <39 years, body mass index of <35 kg/m(2), failure to ovulate with 150 mg of clomiphene citrate for 5 days in the early follicular phase, >12 months of infertility, and no other causes of infertility. INTERVENTION(S): Laparoscopic ovarian diathermy versus three cycles of urinary or recombinant gonadotropins. MAIN OUTCOME MEASURE(S): Cumulative pregnancy and miscarriage rates. RESULT(S): Cumulative pregnancy rates were 28% at 6 months for laparoscopic ovarian diathermy and 33% for three cycles of ovulation induction with gonadotropins. There were three miscarriages in each group. Women in the laparoscopic ovarian diathermy arm of the study had four additional spontaneous pregnancies 6 to 12 months after surgery. CONCLUSION(S): There was no statistically significant difference in pregnancy or miscarriage rates during the 6-month follow-up period or the three cycles. Laparoscopic ovarian diathermy is a safe and effective alternative to ovulation induction with gonadotropins.     

Cost effectiveness of letrozole and purified urinary FSH in treating women with clomiphene citrate-resistant polycystic ovarian syndrome: a randomized controlled trial

We aimed to compare the cost effectiveness of letrozole versus purified urinary follicle stimulating hormone (FSH) in treating patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). This was a randomized trial conducted in Cairo University and Beni-Suef University Hospitals, Egypt. A cohort of 140 eligible women was randomized to receive either letrozole 2.5?mg twice daily for five days, or FSH using a graduated regimen starting with a dose of 75?IU. Treatment was repeated for three months if pregnancy did not occur. There were no significant differences between the two treatments in the cumulative clinical pregnancy rate (30% vs. 34%; p?=?0.578), cumulative ovulation rate (47% vs. 57%; p?=?0.236), miscarriage rate (9% vs. 4%, p?>?0.999) or multiple pregnancy rate (0% and 8%, p?=?0.491) but the FSH cycles were 4.8 times more expensive. Letrozole and FSH were both effective in treating women with CC-resistant PCOS but letrozole was more cost effective.Study registration number: NCT02304107.     

Foley尿管水囊促宫颈成熟用于足月妊娠引产的前瞻性随机对照研究

目的 比较Foley尿管水囊与普贝生栓促宫颈成熟用于足月妊娠引产的安全性和有效性. 方法 采用前瞻性随机对照研究方法,选择2009年6月至12月在本院待产的孕足月、单胎头位、有引产指征、阴道清洁度≤Ⅱ度、胎膜完整、官颈Bishop评分＜6分的初产妇,签署随机对照研究知情同意书后,随机分为2组,最终纳入分析的共126例,分别予Foley尿管水囊(64例)和普贝生栓(62例)促官颈成熟,Foley尿管水囊组与普贝生栓组孕妇的孕周、引产前宫颈评分、引产指征差异无统计学意义.采用t、x2检验或Fisher精确概率法比较2组孕妇的引产成功率、分娩方式、产程时间及母儿结局. 结果 Foley尿管水囊组与普贝生栓组宫颈评分改善、引产成功率、阴道分娩率、总产程、产后出血量差异均无统计学意义(P＞0.05).Foley尿管水囊组较普贝生栓组引产24 h内阴道分娩率低[28.1％(18/64)与56.5％(35/62),t=10.37,P＜0.05],宫缩过频过强发生率也较低[0.0％(0/64)与17.7％(11/62),P＜0.05],但缩宫素使用率高[87.5％(56/64)与21.0％(13/62),x2 =56.27,P＜0.05].2组新生儿Apgar评分、羊水胎粪污染发生率、新生儿体重差异均无统计学意义(P＞0.05).2组孕妇无一例发生产褥感染. 结论 严格掌握Foley尿管水囊促宫颈成熟的指征及执行无菌操作规程,可以取得与普贝生栓相似的促官颈成熟效果及引产母婴结局,未发生过频过强官缩,具有安全性高及成本低廉等优点.     

Luteal phase clomiphene citrate for ovulation induction in women with polycystic ovary syndrome: a systematic review and meta-analysis

Objective: To assess the efficacy of late luteal phase clomiphene citrate (CC) administration relative to early follicular phase CC for ovulation induction for polycystic ovary syndrome (PCOS).

Study design: Review.

Materials and methods: A complete electronic databases including PubMed, Embase, The Cochrane Library, Web of Science, and CBM were searched for relevant randomized controlled trials (RCTs). The search was not restricted by language and publication time. Two reviewers selected trials and assessed trial quality by the Cochrane Handbook 5.1.0 independently.

Results: Four eligible RCT studies involving 708 women (934 cycles) were included. The results of the Meta-analysis: Late luteal phase group was associated with a number of higher total follicles (MD 1.82; 95% CI 0.86–2.78, p?p?p?=?0.26), ovulation rate (RR 0.99; 95% CI 0.86–1.14, p?=?0.87), and abortion rate (RR 1.12; 95% CI 0.38 to 3.29, p?=?0.84) between the two groups.

Conclusion: It appeared that late luteal phase CC for ovulation induction might be an effective method for ovulation induction in women with PCOS compared to conventional CC administration. Further intensive randomized-controlled studies should be warranted to define the efficacy of CC used in late luteal phase.     

来曲唑、他莫昔芬和氯米芬治疗多囊卵巢综合征不孕疗效比较

目的比较多囊卵巢综合征(PCOS)不孕患者经纠正内分泌代谢紊乱后应用3种不同促排卵药物的效果及对子宫内膜的影响。方法选择2009年3月至2010年1月中山大学孙逸仙纪念医院妇产科生殖中心128例PCOS不孕患者,于本院行第1次促排卵,有高雄激素或胰岛素抵抗者经预处理至少3个月。随机分为3组,来曲唑44个周期、他莫昔芬40个周期和氯米芬44个周期。结果月经第10天的子宫内膜厚度,他莫昔芬组[(6.4±1.2)mm]高于来曲唑组[(5.4±1.7)mm]和氯米芬组[(5.4±1.3)mm](P=0.01);HCG日血雌二醇(E2)水平,来曲唑组[(838.6±678.2)pmol/L]低于他莫昔芬组[(2629.2±1931.5)pmol/L]和氯米芬组[(1971.2±1222.8)pmol/L](P<0.001);3组间加用尿促性腺激素(HMG)周期数,HCG日子宫内膜厚度、血黄体生成素及孕酮、直径≥18mm成熟卵泡数,妊娠率和早期流产率,差异无统计学意义(P>0.05);HCG日子宫内膜的厚度与注射HCG的月经周期日及月经第10天的子宫内膜厚度呈正相关(P<0.05),与药物的种类及HCG日血E2水平等无显...     

口服布洛芬治疗早产儿动脉导管未闭的前瞻性随机对照研究

目的 研究口服布洛芬在早产儿动脉导管未闭(patent ductus arteriosus,PDA)治疗中的安全性、治疗效果和副作用,以评估其在早产儿PDA治疗中的应用价值.方法 采用前瞻性随机对照研究方法,根据PDA诊断的时间顺序,按随机数字顺序表,将74例PDA早产儿随机分为布洛芬治疗组(36例)与对照组(38例),布洛芬治疗方法为口服布洛芬混悬液每剂10 mg/kg,间隔24 h 1次,共3次;记录并比较2组PDA的关闭率、相关副作用及患儿住院期间的情况.结果 布洛芬治疗组PDA关闭率为52.8%(19/36),高于对照组(18.4%,7/38),差异有统计学意义(χ2=9.575,P=0.002).在口服布洛芬治疗期间,患儿未出现少尿、肾功能损害、出血倾向、胃肠道穿孔、Ⅲ或Ⅳ级脑室内出血或出血加重等严重副作用,布洛芬治疗组和对照组出现腹胀或胃潴留的发生率分别为33.3%(12/36)和26.3%(10/38),差异无统计学意义(χ2=0.436,P=0.509).布洛芬治疗组患儿平均住院(22.8±14.8) d,用氧(8.3±9.3) d,5.6%(2/36)需要机械通气,与对照组[分别为(24.1±17.1) d、(8.8±8.3) d和2.6%(1/38)]比较差异均无统计学意义(P均＞0.05).结论 口服布洛芬对早产儿PDA有较好的治疗效果,且无明显合并症或副作用发生,应用方便,安全性较高.

Abstract：

Objective To assess the safety, efficacy, temporary side effects and feasibility of oral ibuprofen suspension in the treatment of patent ductus arteriosus (PDA) with hemodynamic significance in premature infants. Method A randomized controlled trial including seventy-four premature infants with PDA was performed from February 2007 to May 2008. Infants were randomly assigned to two groups: testing group (36 patients) received three doses of oral ibuprofen suspension (10 mg/kg at 24-hour intervals) and control group (38 patients) did not receive such treatment. The cure rate of PDA, relative side effects of ibuprofen and complications during treatment were recorded.Results The closure rate of ductus arteriosus in the testing group was 52.8% (19/36), which was higher than that of control group (18.4%, 7/38) (χ2=9.575, P=0.002). The severe side effects did not occur in testing group, such as oliguria, renal impairment, prone of bleeding, gastrointestinal perforation and novel appearing or deteriorative of intraventricular hemorrhage (IVH). Compared with the infants in control group (26.3%, 10/38), the morbidity of abdominal distension or gastric retention in testing group (33.3%, 12/36) was higher, while there was no statistically significant difference (χ2=0.436, P=0.509). The hospital stay [(22.8±14.8) d vs (24.1±17.1) d], mechanical ventilation rate [5.6% (2/36) vs 2.6% (1/38)] and oxygen supplement time [(8.3±9.3) d vs (8.8±8.3) d] between the testing and control groups remained no significant difference (P>0.05). Conclusions Oral ibuprofen suspension could be effective in closing PDA of preterm infants; no significant complications and side-effects occurred during oral ibuprofen treatment. It is suggested that oral ibuprofen suspension treatment was safe, effective and well tolerated for preterm infants with PDA.     

No more surrogate end-points in randomised trials: the PCOSMIC trial protocol for women with polycystic ovary syndrome using metformin for infertility with clomiphene

Current data supporting the effectiveness of metformin as a fertility treatment for women with polycystic ovary syndrome have been misinterpreted. Still unproven for women with polycystic ovary syndrome is, first, whether metformin adds to the standard first-line fertility management in all women, second, whether metformin is an effective fertility treatment for overweight women, and third, the relative fertility efficacy of metformin and clomiphene citrate as a first-line treatment in women with a lower body weight. The PCOSMIC (polycystic ovary syndrome: metformin for infertility with clomiphene) trial is an ongoing New Zealand multicentre double-blind placebo-controlled parallel randomised trial assessing these questions.     

Vaginal repair with mesh versus colporrhaphy for prolapse: a randomised controlled trial

Objective  To compare vaginal repair augmented by mesh with traditional colporrhaphy for the treatment of pelvic organ prolapse.
Design  Prospective randomised controlled trial.
Setting  Tertiary teaching hospital.
Population  One hundred and thirty-nine women with stage ≥2 prolapse according to the pelvic organ prolapse quantification (POP-Q) system requiring both anterior and posterior compartment repair.
Methods  Subjects were randomised to anterior and posterior vaginal repair with mesh augmentation (mesh group, n  = 69) or traditional anterior and posterior colporrhaphy (no mesh group, n  = 70).
Main outcome measures  The primary outcome was the absence of POP-Q stage ≥2 prolapse at 12 months. Secondary outcomes were symptoms, quality-of-life outcomes and satisfaction with surgery. Complications were also reported.
Results  For subjects attending the 12-month review, success in the mesh group was 81.0% (51 of 63 subjects) compared with 65.6% (40/61) in the no mesh group and was not significantly different ( P -value = 0.07). A high level of satisfaction with surgery and improvements in symptoms and quality-of-life data were observed at 12 months compared to baseline in both groups, but there was no significant difference in these outcomes between the two groups. Vaginal mesh exposure occurred in four women in the mesh group (5.6%). De novo dyspareunia was reported by five of 30 (16.7%) sexually active women in the mesh group and five of 33 (15.2%) in the no mesh group at 12 months.
Conclusion  In this study, vaginal surgery augmented by mesh did not result in significantly less recurrent prolapse than traditional colporrhaphy 12 months following surgery.     

Total dose iron dextran infusion versus oral iron for treating iron deficiency anemia in pregnant women: a randomized controlled trial

Study objective: To test safety, efficacy, and cost-effectiveness of total dose infusion (TDI) of low molecular weight (LMW) iron dextran for treatment of iron deficiency anemia (IDA) during pregnancy in comparison to oral ferrous fumarate.

Design: Prospective interventional randomized controlled trial (RCT). Design classification. Canadian Task Force II3.

Setting: Antenatal clinic and causality unit of a tertiary care referral facility and University Hospital.

Patients: A total 66 anemic pregnant women (hemoglobin level between 7–10?g/dl).

Intervention: Administration of a LMW iron dextran as a TDI (group A) or Oral iron ferrous fumarate 60?mg elemental iron three times daily (group B) followed by remeasurement of hemoglobin after 4 weeks.

Measures and main results: The main outcome measure was clinical and laboratory improvement of anemia after 4 weeks of starting the therapy. Both groups showed a significant clinical improvement of anemia 4 weeks post-therapy. However, the first improvement of symptoms was significantly faster in group A. Complete blood count (CBC) as well as all iron indices were improved in both groups after 4 weeks of therapy, but were significantly better in group A than B. Side effects in group B were mainly gastrointestinal (GIT) while one case of mild hypersensitivity to TDI and another one case of local reaction at the site of injection were reported in group A.

Conclusions: It is concluded that despite being equally effective in improving both clinical and laboratory evidence of IDA, TDI allows iron restoration with a single dose faster than oral iron therapy with a reasonable safety profile. It is a good example of office one-stop therapy. Nevertheless, noninvasive selfusage at home is a clear advantage of the cheaper oral iron therapy which makes it the first choice for treating IDA in the second and third trimesters of pregnancy in tolerable cases.

Trial registration: ClinicalTrials.gov identifier: NCT03212781.