Clinical trial NCT05168865: Letrozole Versus Hormonal Preparation in Frozen Cycles of PCOS Patients.
Official title: Letrozole Versus Hormonal Preparation in Frozen Cycles of PCOS Patients. Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Frozen Embryo Transfer
Polycystic Ovarian Disease
Letrozole
Hormone Replacement Therapy
Live Birth
Miscarriage
Lead sponsor: Dubai Fertility Center
Sponsor class: OTHER
First posted: 2021-12-23
Enrollment: 0
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* Women \> 40 years old or younger than 20.
* 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.

Primary outcomes:
measure: livebirth rate per embryo transfer
timeFrame: 9 months
Secondary outcomes:
measure: miscarriage rate per embryo transfer
timeFrame: 6 months
measure: ongoing pregnancy per embryo transfer
timeFrame: 3 months
Other outcomes:
Locations:
Study officials:
References: