An interventional study of IUI or intercourse in Letrozole, Clomiphene Citrate and Ovulation Disorder, sponsored by Mỹ Đức Hospital. Recruiting at 1 site in Vietnam. Open to female participants aged 18 Years to 40 Years. Per ClinicalTrials.gov, last updated 2026-10-20.
Sponsored by Mỹ Đức Hospital · Not applicable, Interventional, and Treatment
This randomized controlled trial (RCT) aims to evaluate whether, in infertile women with WHO II/IV ovulatory disorders, a combination of letrozole (LE) and clomiphene citrate (CC) compared to LE alone, result in higher live birth rates.
The study is designed as an open-label, multicenter RCT across six fertility clinics in Vietnam. Participants will be randomized into two groups: (1) LE + CC , (2) LE alone. The primary outcome measure is the live birth rate after one treatment cycle. Based on prior data, the live birth rate for IUI in letrozole cycles is estimated at 12%. To detect a 10% increase in live birth rates with CC, 436 couples are needed (α = 0.05, power = 80%). Additionally, the live birth rate after IUI with LE-induced ovulation is approximately 18.7% (Diamond et al., 2015). To detect a 10% increase with CC, 560 couples are required (α = 0.05, power = 80%). Considering a 5% loss to follow-up and protocol deviations, the study plans to recruit 600 participants (150 per arm).
Letrozole (LE) has been suggested as a first-line treatment for ovulation induction in PCOS. Clomiphene citrate (CC) is another widely used drug to induce ovulation in women with PCOS. Due to the different mechanisms of action of CC and letrozole, it is possible that taking these drugs together may increase the ovulation rate by having a synergistic effect with their own mechanisms and resulting to increase the pregnancy outcome of patients undergoing ovulation induction (OI).
Mejia et al. conducted a randomized controlled trial (RCT) and reported the ovulation rate was significantly higher in the combination group than in the LE-alone group (N=70, 77% vs. 42.9%, respectively; RR 1.80 95%. CI. 1.18 to 2.75, P=0.007). This finding is confirmed by another RCT but not in a third more recent RCT, with larger sample size. Live birth rate was only reported as secondary endpoint in two studies, with a non-significant difference between the two groups [12% vs. 7%, RR 1.68, 95% CI 0.19 to 14.66) and 16.4% vs. 18.6%, RR 0.92, 95% CI 0.57 to 1.50)]. Therefore, the investigators plan an RCT to evaluate whether a combination of LE and CC results in higher live birth rates than LE alone in women with WHO II/IV ovulatory disorders.
This is a open-label, multicenter, randomized controlled trial across six fertility clinics in Vietnam. Potentially eligible participants will be given a study information sheet during their first consultation, at least 2 weeks before the start of the menstrual cycle, whether spontaneous or induced. In case the women present to the clinic during their menstrual cycle and wish to start treatment straightaway, they will be given the information sheet to read while waiting for the clinicians. Screening for eligibility will be performed by treating physicians on the day OI starts. Eligible participants will be invited to a full discussion with investigators about the study. Women who fulfil the eligibility criteria and who have been counselled before will be formally invited to participate in the study. If the women agree to participate, they will be asked to sign the informed consent form. After informed consent, a fasting blood sample will be obtained for hormone and biochemical analysis.
Participants will be randomized in a 1:1 ratio to receive the combination of LE and CC (LE+CC) and LE alone. The computer-generated random list will be prepared by an independent statistician who has no other involvement in the study. Assignment to treatment allocation will be done via a web portal hosted by HOPE Research Center, Vietnam. The randomization schedule will be computer-generated at HOPE Research Center, with a permuted random block size of 4 and 8.
Combination of LE and CC group: 5 milligrams LE per day (Femara® 2.5 milligrams, Novartis, Switzerland) and 50 milligrams CC (Duinum 50 milligrams, Medochemie, Cyprus) per day, starting on the second to the fourth day of the cycle, for five consecutive days.
LE alone group: 5 milligrams LE per day (Femara® 2.5 milligrams, Novartis, Switzerland), starting on the second to the fourth day of cycle, for five consecutive days.
IUI or natural intercourse will be indicated based on the physicians and patients.
The primary endpoint will be live birth after one treatment cycle.
Mỹ Đức Hospital is the lead sponsor of 56 studies on the registry; 21 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
5 milligrams LE per day (Femara® 2.5 milligrams, Novartis, Switzerland) and 50 milligrams CC (Duinum 50 milligrams, Medochemie, Cyprus) per day, starting on the second to the fourth day of the cycle, for five consecutive days.
Procedure: IUI or intercourse
5 milligrams LE per day (Femara® 2.5 milligrams, Novartis, Switzerland), starting on the second to the fourth day of cycle, for five consecutive days.
Procedure: IUI or intercourse
5 milligrams LE per day (Femara® 2.5 milligrams, Novartis, Switzerland) and 50 milligrams CC (Duinum 50 milligrams, Medochemie, Cyprus) or 5 milligrams LE per day (Femara® 2.5 milligrams, Novartis, Switzerland) will be started on the second to the fourth day of the cycle, for five consecutive days. An ultrasound will be carried out three days after the last dose of medicine (day 8 of OI) to evaluate ovarian follicles' growth and the endometrium's thickness. If the follicular diameter reach ≥14 millimetres, check-up will be planned every two days until it reaches 18 millimetres. If there is the appearance of at least one follicle reaching 18 millimetres or more, a human chorionic gonadotropin (hCG) injection (IVF-C 5000 IU, LG Life Science, Korea) will be administered on the same day of the ultrasound in order to induce ovulation. IUI will be scheduled 36 - 38 hours after hCG injection or intercourse will be scheduled in the next day.
Live birth after one treatment cycle
Live birth will be defined as the complete expulsion or extraction from a woman of a product of fertilization, after 22 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heart beat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached.
Time frame: At 22 weeks of gestation
Duration of stimulation
Duration of stimulation
Time frame: During the intervention
Number of follicles ≥14mm on day of hCG
Number of follicles ≥14mm on day of hCG
Time frame: During the intervention
Endometrial thickness on day of hCG
Endometrial thickness on day of hCG
Time frame: During the intervention
Cycle cancellation
The cycle will be cancelled if (1) there is no follicle reaches ≥18 millimetres) on day 21 of the OI; (2) there are ≥ 3 follicles with diameter ≥16 millimetres or (3) ≥ 4 ovarian follicles with diameter ≥10 millimetres
Time frame: At 21 day of the ovulation induction cycle
Ovulation
A serum midluteal progesterone (17-OH-progesterone) will be measured on day 7 after the hCG injection. A level of \>3 ng/mL (\>9.5 nmol/L) will be used as evidence of ovulation.
Time frame: At day 7 after the hCG injection
Positive pregnancy test
Serum human chorionic gonadotropin level greater than 25 mIU/mL at day 15 after IUI or timed intercourse
Time frame: At day 15 after IUI or timed intercourse
Clinical pregnancy
Diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy at 6 weeks or more. In addition to intra-uterine pregnancy, it includes a clinically documented ectopic pregnancy
Time frame: After 6 weeks of gestation
Ongoing pregnancy
Pregnancy with a detectable heart rate at 12 weeks gestation or beyond
Time frame: After 12 weeks of gestation
Multiple pregnancies
The presence of more than one sac at early pregnancy ultrasound (6-9 weeks gestation)
Time frame: At 6-9 weeks of gestation
Multiple birth
The complete expulsion or extraction from a woman of more than one fetus, after 22 completed weeks of gestational age, irrespective of whether it is a live birth or stillbirth
Time frame: At 22 weeks of gestation
Ectopic pregnancy
A pregnancy outside the uterine cavity, diagnosed by ultrasound, surgical visualization or histopathology
Time frame: At 7 weeks of gestation
Miscarriage <22 weeks
Spontaneous loss of pregnancy up to 22 weeks of gestation
Time frame: Before 22 completed weeks of gestation
Gestational age at delivery
Gestational age at delivery
Time frame: At the time of delivery
Growth restriction
a birth weight \< 10th percentile
Time frame: At the time of delivery
Stillbirth
The death of a fetus prior to the complete expulsion or extraction from its mother after 20 completed weeks of gestational age. The death is determined by the fact that, after such separation, the fetus does not breathe or show any other.
Time frame: After 20 completed weeks of gestational age
Premature birth
Multiple definitions, defined as delivery at \<24, \<28, \<32, \<37 completed weeks
Time frame: At 22, 28, 32 weeks and 37 weeks of gestation
Onset of labour
Onset of labour
Time frame: At the time of delivery
Mode of delivery
Mode of delivery
Time frame: At the time of delivery
Birth weight
Weight of singletons and twins
Time frame: At the time of delivery
Low birth weight
Weight \< 2500 gm at birth
Time frame: At the time of delivery
Very low birth weight
Weight \< 1500 gm at birth
Time frame: At the time of delivery
High birth weight
Weight 4000 gm or 4500 gm at birth
Time frame: At the time of delivery
Very high birth weight
Weight over than 4.500 g for women with diabetes, and a threshold of 5000 g for women without diabetes
Time frame: At the time of delivery
Gestational diabetes mellitus
GDM is diagnosed using a 75g oral glucose tolerance test
Time frame: At 24 to 28 weeks of gestation
Hypertension in pregnancy
Pregnancy-induced hypertension, pre-eclampsia, eclampsia and HELLP syndrome
Time frame: after 20 weeks of gestation or beyond
Congenital abnormalities
Structural or functional disorders that occur during intra-uterine life and can be identified prenatally, at birth or later in life. Congenital anomalies can be caused by single gene defects, chromosomal disorders, multifactorial inheritance, environmental teratogens, and micronutrient deficiencies. The time of identification should be reported
Time frame: At birth
Neonatal mortality
Death of a live-born baby within 28 days of birth
Time frame: within 28 days of birth
NICU admission
The admittance of the newborn to NICU
Time frame: At birth
Reported side-effects
included headache, hot flashes, abdominal bloating, abdominal pain including cramps, nausea, mood changes, fatigue, back pain, dizziness, breast discomfort, diarrhoea, night sweats, sleep disturbances
Time frame: During the intervention
Hospitalized or seek any additional care during the ovulation induction cycle
Hospitalized or seek any additional care during the ovulation induction cycle
Time frame: During the intervention
Incidence of Ovarian hyperstimulation syndrome (OHSS)
A potentially lethal iatrogenic complication of the early luteal phase or/and early pregnancy after OI or ovarian stimulation. OHSS was evaluated if symptoms were reported by the patient. OHSS was classified using the flow diagram
Time frame: 10 days after the intervention
Plan to share: Yes
Started Apr 2025 (actual). Primary completion is estimated for Jun 2027, 26 months after the start.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Mỹ Đức Hospital