Development of safe and convenient ovulation induction

不孕妇女使用促性腺激素诱导排卵需要每天到医院接受注射，并且与多胎妊娠高度相关。我们开发并评价了促卵泡素（FSH）-促性腺激素释放激素（GnRH）脉冲（F-G）、慢性低剂量FSH自身注射（LD-F）和克罗米芬-二甲双胍（Cl-Met）诱导排卵的新方法。研究设计为前瞻性、随机化和交叉研究。F-GWe比较了F-G和LD-F在10例PCOS患者中的疗效和安全性。LD-F时间表：F-G给药方案：FSH开始每天注射75 IU，14 d后无卵泡时增加剂量，FSH开始每天注射150 IU，卵泡长至11 mm时改为GnRH脉冲给药。两种治疗方法同样有效。F-G组每个周期的住院总天数（8.8± 1.3天，平均值±标准差）显著短于LD-F组（17.7± 6.6天，P<0.01）.对3例无排卵患者进行了LD-F，分别采用自身注射法（SI）和住院治疗法（AH）。两组均获得单次排卵，无不良反应。卵泡成熟的总天数在SI中为6.0 ±1.0天，在AH中为17.7± 8.0天（p=0.067）。Cl-Met我们比较了Cl和Cl-Met在5名克罗米芬（100 mg）耐药的PCOS女性中的疗效和安全性。克罗米酚的剂量为150 mg/天，二甲双胍的剂量为750 mg/天（第5天至卵泡成熟）。Cl组4例中有1例排卵，Cl-Met组5例中有4例排卵。所有周期均达到单次排卵。其中2例Cl-Met（单胎）成功妊娠。总之，所有新方法对于不孕患者来说都是安全且全面的方法。

Ovulation induction using gonadotropin for infertile women requires daily attendance to hospital for injection, and is highly associated with multiple pregnancies. We developed and evaluated new method to induce ovulation: FSH-pulsatile GnRH(F-G), chronic low-dose FSH self-injection(LD-F) and clomiphene-metformine(Cl-Met). Study designs were prospective randomized and cross over in all investigations.1. F-GWe compared efficacy and safety between F-G and LD-F in 10 PCOS patients. Schedule of LD-F: Daily injection of FSH was started with a dose of 75 IU and increased after 14 days treatment in case no follicle developed.Schedule of F-G: Daily injection of FSH was started with a dose of 150 IU and switched to pulsatile GnRH administration when follicle reached 11mm. Both treatments were equally effective. Total day of attendance to hospital per cycle was significantly shorter in F-G(8.8± 1.3 days, mean±SE) than in LD-F(17.7± 6.6) (P<0.01).2. LD-F by self-injectionLD-F was performed by self-injection(SI) or by attendance to hospital(AH) to 3 anovulatory patients. All cycles of both treatment achieved single ovulation, and no side effect was observed. Total days of attendance to follicular maturation were 6.0 ±1.0 clays in SI and 17.7± 8.0 days in AH (p=0.067).3. Cl-MetWe compared efficacy and safety between Cl and Cl-Met in 5 clomiphene (100mg)-resistant women with PCOS. Dose of clomiphene was 150 mg/day and dose of metformin was 750 mg/day(day5 to follicular maturation). One out of 4 in Cl, and 4 out of 5 in Cl-Met showed ovulation. All cycles achieved single ovulations. Pregnancies were achieved in 2 of Cl-Met(singletons).In conclusion, all of new methods were safe and comprehensive methods for infertile patients.