Extension of the clomiphene citrate stair-step protocol to gonadotropin treatment in women with clomiphene resistant polycystic ovarian syndrome

Abstract

Our objective was to evaluate the safety and efficacy of direct initiation of gonadotropin ovarian stimulation without prior withdrawal bleeding in anovulatory clomiphene citrate (CC) resistant polycystic ovarian syndrome (PCOS) patients. Eighteen PCOS patients underwent ovulation induction with CC using a stair-step regimen. Patients who failed to respond to the maximal dose of CC initiated gonadotropin stimulation without inducing withdrawal bleeding, using the chronic low dose regimen. The primary outcome measure was the time to ovulation from the beginning of CC treatment until the day of ovulatory trigger. This was compared with the time to ovulation calculated according to the traditional approach, which includes inducing progesterone withdrawal bleeding between each CC dose increment and before gonadotropin therapy. The time to ovulation in the study group was 67.0 ± 6.8 days. The estimated time to ovulation according to the traditional approach was approximately 110 days. The clinical pregnancy rate was 44% (8/18), and all pregnancies were singletons. One patient miscarried; hence the live birth rate was 38.9% (7/18). Direct initiation of gonadotropin therapy without prior induction of withdrawal bleeding in clomiphene resistant PCOS patients results in considerable reduction of the time to ovulation and is both safe and efficacious.

Chinese abstract

我们的目的是评估先前无撤退性出血的无排卵克罗米芬（CC）抵抗的多囊卵巢综合征（PCOS）患者直接启动促性腺激素卵巢刺激的安全性和有效性。 18例PCOS患者用CC梯度式方案进行诱导排卵。未能对CC的最大剂量启动促性腺激素刺激作出反应且无撤退性出血的患者用慢性低剂量方案。 主要结局指标是从CC开始治疗到排卵当天的时间。与根据传统方法计算的排卵时间进行比较, 其包括在每次CC剂量增加之间及促性腺激素治疗之前的诱导孕激素撤退性出血的时间。研究组排卵时间为67.0 ± 6.8天。按照传统方法估计的排卵时间约为110天。临床妊娠率为44%（8/18）, 所有妊娠均为单胎。一例病人流产, 因此活产率为38.9%（7/18）。直接启动促性腺激素治疗, 无需先前诱导克罗米芬耐药性PCOS患者的撤退性出血, 导致排卵时间大大减少, 既安全又有效。

Keywords:

• Clomiphene citrate
• gonadotropins
• ovulation induction
• polycystic ovarian syndrome
• withdrawal bleeding

Declaration of interest

The authors report no conflicts of interest.