The comparison of letrozole with estradiol on the outcomes of frozen embryo transfer cycles in women with polycystic ovarian syndrome
Design
A randomized controlled clinical trial, with parallel groups, single blinded, phase 3, with simple randomization method on 510 patients.
Settings and conduct
This study will be carried out at Yas Hospital (Tehran,
Iran) on women with polycystic ovarian syndrome. The patients, the sonographer and the physician who will be responsible for administration of drugs will know about the interventions; the physician who will be responsible for embryo transferring and the statistician are unaware of the interventions.
Participants/Inclusion and exclusion criteria
Inclusion criteria of study: The women with polycystic ovarian syndrome; 18 - 40 years old; candidate of frozen embryo transfer
Exclusion criteria of study: The other causes of hyperandrogenism and ovarian dysfunction; Basal FSH level >10 IU/L; History of recurrent miscarriage; History of congenital or acquired uterine malformations; History of male factor infertility
Intervention groups
In the control group, endometrial preparation will be done by traditional method with estrogen and progesterone containing drugs.
In the study group, endometrial preparation will be done by letrozole.
Main outcome variables
Live Birth Rate
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20150105020558N3
Registration date:2021-03-02, 1399/12/12
Registration timing:prospective
Last update:2021-03-02, 1399/12/12
Update count:0
Registration date
2021-03-02, 1399/12/12
Registrant information
Name
Mahbod Ebrahimi
Name of organization / entity
Tehran University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 21 8882 7794
Email address
maebrahimi@tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-04-21, 1400/02/01
Expected recruitment end date
2022-10-22, 1401/07/30
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Comparison of the Effectiveness of Letrozole with Estradiol on Frozen Embryo Transfer Cycle Outcomes in Women with Polycystic Ovarian Syndrome
Public title
Letrozole effect in IVF cycles
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
The patients with impression of polycystic ovarian syndrome according to Rotterdam consensus as fulfilling at least two of the three criteria: 1- oligo/anovulation; 2- clinical or biochemical signs of hyperandrogenism; and 3- polycystic ovarian morphology on ultrasound
Female age: 18 - 40 years old
The candidate of frozen embryo transfer
Exclusion criteria:
The other causes of hyperandrogenism and ovarian dysfunction
Basal FSH level >10 IU/L
History of recurrent miscarriage
History of congenital or acquired uterine malformations
History of male factor infertility
Age
From 18 years old to 40 years old
Gender
Female
Phase
3
Groups that have been masked
Care provider
Outcome assessor
Data analyser
Sample size
Target sample size:
510
Randomization (investigator's opinion)
Randomized
Randomization description
Random allocation, there are 255 small envelopes containing letter A and 255 small envelopes in the same shape containing letter B in a bag; and for each patient one envelope is selected randomly.
Blinding (investigator's opinion)
Single blinded
Blinding description
Whilst the patients, the sonographer and the physician who will be responsible for administration of drugs will know about the interventions; the physician who will be responsible for embryo transferring and the statistician are unaware of the interventions.
The number of deliveries that resulted in a live born neonate, expressed per 100 embryo transfers
Secondary outcomes
1
Description
Clinical Pregnancy Rate
Timepoint
4 to 6 weeks after frozen embryo transfer
Method of measurement
A visible gestational sac by transvaginal ultrasound
2
Description
Ongoing Pregnancy Rate
Timepoint
After 20th weeks of pregnancy
Method of measurement
The number of fetuses with heart activity beyond 20 weeks of gestation
3
Description
Cycle cancellation rate
Timepoint
from 15th until 21th days of cycle
Method of measurement
The number of cancelled cycles
4
Description
Endometrial thickness
Timepoint
On the day of HCG injection
Method of measurement
The measuring of endometrial thickness by transvaginal ultrasound
5
Description
Abortion rate
Timepoint
From 5th until 24th gestational weeks
Method of measurement
The detection of lack or loss of fetal heart activity by ultrasound
6
Description
Premature delivery rate
Timepoint
From 25th until 36th gestational weeks
Method of measurement
The delivery of fetus(es)
Intervention groups
1
Description
Intervention group: In this group, two letrozole tablets (2.5 mg, َAburaihan pharmaceutical co) is prescribed orally for 5 days initiating on day 3 of spontaneous menses or progesterone-induced withdrawal bleeding. Ultrasound monitoring are performed from cycle day 10 onwards. if the leading follicle reaches a mean diameter of ≥ 14mm on cycle day 10, ultrasound is repeated every 2 days. In case of a mean dominant follicle diameter < 14mm on day 10, a daily dosage of 75 IU hMG is supplemented to stimulate follicle growth. When the dominant follicle reaches a mean diameter of ≥17mm and endometrial thickness reaches ≥ 7mm, a bolus of urinary hCG 5000 IU will be injected. According to embryo staging (cleavage stage or blastocyst), embryo transferring will be scheduled 4 or 6 days later.
Category
Treatment - Drugs
2
Description
Control group: In this group, three Estradiol Valerate tablets (2 mg, َAburaihan pharmaceutical co) are prescribed orally from day 3 of spontaneous menses or progesterone-induced withdrawal bleeding. Ultrasound monitoring are performed 12 to 14 days later. ultrasound examination is carried out to measure endometrial thickness as well as to ensure there is no dominant follicle. When the endometrial thickness attained ≥ 7mm, progestrone vaginal suppositories (Fertigest, 400mg, Aburaihan pharmaceutical co) twice daily are initiated. According to embryo staging (cleavage stage or blastocyst), embryo transferring will be scheduled 4 or 6 days later.