Letrozole Versus Hormonal Preparation in Frozen Cycles of PCOS Patients. Randomized Controlled Study
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 发起方
- 主要终点
- livebirth rate per embryo transfer
研究概览
简要总结
One of the indications of freezing is to reduce the risk of ovarian hyperstimulation syndrome particularly in polycystic ovarian disease (PCOS) women. Very few RCTs addressed the issue of optimizing the endometrium for a frozen cycle. Interestingly, Letrozole for ovarian stimulation showed significantly better reproductive outcome when compared with hormone replacement therapy (HRT) cycle. In addition, HRT cycle has been associated with higher miscarriage rate when compared with natural cycle frozen embryo transfer. Nevertheless, there is not yet a well-designed prospective randomized study comparing letrozole and HRT in PCOS women undergoing frozen embryo transfer.
详细描述
Freezing oocytes and embryos has become an integral part of the daily IVF practice. One of the indications of freezing is to reduce the risk of ovarian hyperstimulation syndrome particularly in polycystic ovarian disease (PCOS) women.
Very few randomized control trials addressed the issue of optimizing the endometrium for a frozen cycle. As PCOS women do not regularly ovulate, most of their frozen cycles are conducted after hormonal replacement therapy (HRT) preparation of the endometrium or after ovulation induction. In HRT cycle the endometrium is prepared using exogenous estradiol and progesterone. While HRT cycles requires less monitoring and easy scheduling, it is costly, associated with increased risk of thrombosis and women must continue using the exogenous hormones up to 10 to 12 weeks of gestation.
Interestingly, Letrozole for ovarian stimulation showed significantly better reproductive outcome when compared with HRT cycles. In agreement with the previous Chinese study, a retrospective Japanese ART registry data that included 110 722 frozen cycles confirmed the superiority of letrozole. Nevertheless, there is not yet a well-designed prospective randomized study.
In addition, HRT cycle has been associated with higher miscarriage rate when compared with natural cycle frozen embryo transfer. HRT is usually used in patients with PCOS. A retrospective study including 2664 PCOS patients showed significant decrease in the pregnancy loss when letrozole was used when compared with HRT in frozen cycles.
Investigators thought of comparing letrozole and HRT in women with PCOS who are undergoing frozen cycles in PCOS women. Live birth and miscarriage rates will be the primary outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women with PCOS diagnosed with Rotterdam criteria.
- •Age between 20 to 40-year-old
- •Undergoing frozen oocytes intracytoplasmic sperm injection transfer or frozen embryo transfer
- •Willingly accept to participate in the study
排除标准
- •Women > 40 years old or younger than
- •Uterine pathology that decreases the chance of pregnancy or increases risk of miscarriage such as
- •Uterine fibroids (sub-mucous of any size or intramural of > 3 cm)
- •Uncontrolled endocrinal-pathological disease like
- •Cushing syndrome,
- •Adrenal hyperplasia,
- •Hyperprolactinemia,
- •Acromegaly,
- •Thyroid disease,
- •Diabetes mellitus, and
- •Immune disorders.
- •Presence of Hydrosalpinx
- •Not willing or able to sign the consent form.
研究组 & 干预措施
PCOS women will receive letrozole ovarian stimulation.
Polycystic ovarian disease (PCOS) women undergoing frozen embryo transfer (FER) will use Letrozole 5 mg starting on day 3 of spontaneous menstrual period or after progesterone withdrawal bleeding for five consecutive days.
干预措施: Letrozole 2.5mg (Drug)
PCOS women will receive Estradiol and Progesterone (hormonal endometrial preparation).
PCOS women will use daily Cetorelix acetate 0.25 mg injections for 5 days from day 1-3 of the menstrual follow or after progesterone (P4) withdrawal bleeding. They will commence daily oral Estradiol Valerate (E2) 2 mg twice daily for 5 days starting from day 3 of the menstrual flow or after P4 withdrawal bleeding, then-after three times daily. When endometrial thickness reaches 7 mm or more, the dose of E2 will be reduced to 4 mg/ day. Women will start using vaginal micronized P4 100 mg three times daily starting from 8PM. After 48 hours of starting the vaginal P4, oral Dydrogesterone 10 mg three times daily will commence.
干预措施: Letrozole 2.5mg (Drug)
结局指标
主要结局
livebirth rate per embryo transfer
时间窗: 9 months
A birth after 24 weeks gestation with a baby showing signs of life.
次要结局
- miscarriage rate per embryo transfer(6 months)
- ongoing pregnancy per embryo transfer(3 months)
研究者
Mohamed Elkalyoubi
Principal investigator
Dubai Fertility Center