Live Birth After Letrozole-stimulated Cycles Versus Hormone Replacement Treatment Cycles for the First Frozen Embryo Transfer in Women With PCOS

Study Overview
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Brief Summary
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This is a multicenter randomized controlled trial comparing the efficacy and safety of two endometrial preparation protocols for the first frozen embryo transfer cycle in PCOS with whole embryo freezing. Subjects will be randomized to letrozole-stimulated group or hormone replacement treatment group in their first frozen embryo transfer cycle, and their pregnancy and perinatal outcomes during this cycle will be followed up and analysis.

Official Title
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Live Birth After Letrozole-stimulated Cycles Versus Hormone Replacement Treatment Cycles for the First Frozen Embryo Transfer in Women With PCOS: a Randomized Controlled Trial

Conditions
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PCOS

Intervention / Treatment
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* Procedure: Oral Letrozole
* Procedure: Oral estradiol valerate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. women diagnosed with PCOS according to modified Rotterdam criteria; 2. Women who are participating in their first cycle of IVF or ICSI. 3. Women whose IVF/ICSI ovarian stimulation protocol was either GnRH antagonist protocol or long agonist protocol. 4. Women with whole embryos freezing. 5. Women aged 20 to 38 years old; 6. Women BMI 18 kg/m2 to 30 kg/m2 7. Women with at least one good-quality embryo suitable for transfer, including day 3 cleavage stage embryo with grade 7CI /8CI and day 5 or day 6 blastocyst with grade 4BB or higher. Exclusion Criteria: 1. Women who has a history of recurrent spontaneous abortion. 2. Women with unilateral/bilateral oophorectomy. 3. Women with untreated Hydrosalpinx. 4. Women with a uterine cavity abnormality, such as a uterine congenital malformation, untreated uterine septum (except shallow uterine septum), adenomyosis, submucous myoma, or moderate to severe intrauterine adhesions. 5. Women with uncontrolled diabetes mellitus, thyroid disease and hypertension. 6. Women who are indicated and planned to undergo preimplantation genetic test (PGT).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 38 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Letrozole-stimulated group<br> | Procedure: Oral Letrozole<br>* Oral Letrozole at a dose of 2.5mg daily will be started on days 3-5 of the menstrual cycle and will be continued for 5 days.<br>|
| Active Comparator: Hormone replacement treatment group<br> | Procedure: Oral estradiol valerate<br>* Oral estradiol valerate at a dose of 3mg twice daily will be started on days 3-5 of the menstrual cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live birth rate | Number of women with live birth/ number of women randomized to the specific group. Live birth is defined as the delivery of any viable infant at 28 weeks or more of gestation. | 11 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate | Number of women with clinical pregnancy /number of women randomized to the specific group. Clinical pregnancy was defined as the presence of at least one gestational sac in the uterine cavity on ultrasound at about 28 days after embryo transfer. | 2 months | 
| Biochemical pregnancy rate | Number of women with biochemical pregnancy /number of women randomized to the specific group. Biochemical pregnancy was defined as a human chorionic gonadotropin level of more than 10 milli-International unit (mIU) per milliliter (ml) as measured at about 14 days after embryo transfer. | 1.5 months | 
| Miscarriage rate | Number of women with miscarrage / number of women with clinical pregnancy. Miscarriage refers to a complete spontaneous abortion or a nonviable pregnancy before 28 weeks of gestation. | 9 months | 
| Cycle cancellation rate | Number of women who initiated endometrial preparation without embryos transfer / number of women randomized to the specific group. | 1 month | 
| Birth weight | Weight of newborns at delivery. | 11 months | 
| Incidence of obstetric and perinatal complications | Number of pregnancies with complications / number of clinical pregnancies. | 11 months | 
| Incidence of neonatal complications | Number of live births with neonatal complications / number of live births. | 11 months | 
| Ectopic pregnancy rate | Number of women with ectopic pregnancy /number of women randomized to the specific group. Ectopic pregnancy will be defined as implantation outside the uterine cavity, as confirmed by sonography or laparoscopy. | 2 months |