Letrozole Versus Hormonal Preparation in Frozen Cycles of PCOS Patients.

Miscarriage Clinical Trial

Official title:

Letrozole Versus Hormonal Preparation in Frozen Cycles of PCOS Patients. Randomized Controlled Study

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05168865
• Other study ID #: DSREC-09/2020_16
• Status: Withdrawn
• Phase: Phase 4
• Start date: August 1, 2023
• Est. completion date: April 1, 2024

Study information

• Verified date: February 2024
• Source: Dubai Fertility Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 1, 2024
• Est. primary completion date: February 1, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Abortion, Spontaneous
• Frozen Embryo Transfer
• Hormone Replacement Therapy
• Letrozole
• Live Birth
• Miscarriage
• Ovarian Diseases
• Polycystic Ovarian Disease
• Polycystic Ovary Syndrome

Intervention

Drug:
• Letrozole 2.5mg
Letrozole 5 mg starting on day 3 of spontaneous menstrual period or after progesterone withdrawal bleeding for five consecutive days.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Dubai Fertility Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	livebirth rate per embryo transfer	A birth after 24 weeks gestation with a baby showing signs of life.	9 months
Secondary	miscarriage rate per embryo transfer	loss of pregnancy before 24 weeks gestation	6 months
Secondary	ongoing pregnancy per embryo transfer	ongoing viable pregnancy (by ultrasound examination at 12 weeks' gestation)	3 months