Letrozole Versus Gonadotropins in Clomiphene Citrate Resistance

NCT ID: NCT04834791

Last Updated: 2021-04-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-01

Study Completion Date

2019-10-31

Brief Summary

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Clomiphene citrate resistance (CCR) occur in 15-40% in women with PCOS. Several studies have shown that letrozole is superior to CC regarding side effects, ovulation, and pregnancy rates. Letrozole or gonadotropins use for ovulation induction in CCR is not well established which is superior and most safe.

Detailed Description

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This study included 70 patients enrolled according inclusion and exclusion criteria. The inclusion criteria were (a) Infertility lasting one year or more in presence of regular intercourse, (b) Patients' age between 20-35years (c) Normal semen analysis according to WHO 2010 (d) Patent fallopian tubes (e) Normal prolactin and TSH. (e) Anovulatory cycles confirmed by mid-luteal progesterone ≤ 3 ng/ml and (f) Clomiphene citrate resistance for 3 cycles of 150mg. Exclusion Criteria were (a) Any hormonal disturbances eg. hyperprolactinemia, (b) Immunological causes of infertility, (c) Coital errors, (d) Metabolic disorders and (e) Poor patient compliance.

Sample size calculation: The minimum sample size calculated using Epi info program version 7 for unmatched case control study; 80% power and 95% Confidence interval was 22 for each group. For better accuracy and validity of results the sample size was increased by 10%=3 in each group. The total number of cases was 50 and 25 for each group.

Randomization and allocation: It was a prospective quesi-randomization. Based on the attendance order, patients with odd numbers were considered group I (Letrozole group) and those with even numbers were considered group II (Gonadotropin group). Allocation was equal 1:1.

Intervention:

Group I (Letrozole Group n=25): These patients were treated with letrozole (Femara®, Novartis New York, NY, USA) in a dose 2.5 mg (one tablet daily) orally began on the 3rd day to the 7th day of the cycle. If ovulation is not achieved dose is increased by 2.5 mg in next cycle till 3 cycles. If hyperstimulation occurred, the cycle was cancelled and the patients were excluded from the study.

Group II (Gonadotropin Group n=25) These patients were given urofollitropin (fostimon ®, IBSA, Lugano, Switzerland) in a dose of 75 IU/mL I.M from day 3rd to day 7th of the cycle beginning by one ampoule per day and the dose had been modulated according to response. If hyperstimulation occurred, the cycle was cancelled and the patients were excluded from the study.

Methods:

Proper history taking including age, gravidity, parity, infertility duration, history of laparoscopic surgery, previous induction of ovulation in the last 6 months. Examination was done to assess weight, height (BMI), signs of androgen excess, thyroid gland and breast examination.

Serum FSH, LH, testosterone level, prolactin level and thyroid stimulating hormone on day 3 of spontaneous menstrual cycle were done. Serum Progesterone (P4) was done on day 22 (midluteal) to confirm ovulation if ≥ 10ng/ml.

Basal transvaginal U/S on day3 of the cycle to detect criteria of PCOS and count number of antral follicles in both ovaries and to exclude of any basal ovarian cyst. Transvaginal ultrasound was also used to follow follicular growth and endometrial thickness starting on day 8 and then every other day till assuming good ovulatory response when one or more follicles is ≥ 18mm and endometrial thickness ≥ 6mm.

Human Chorionic Gonadotropin (choriomon®, IBSA, Lugano, Switzerland) 10.000IU/I.M was administered when good ovulatory response was assumed. The intercourse was advised on the day of HCG injection and every other day for 4 days after injection HCG.

Number and size of Dominant follicles, endometrial thickness were recorded. Clinical pregnancy was detected by serum pregnancy test and by presence of intrauterine gestational sac with fetal pulsation.

Outcome measures: Primary outcomes was ovulation rate. Secondary outcomes were pregnancy rate.

Conditions

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Clomiphene Citrate Resistance Ovulation Induction Letrozole Gonadotropins

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Letrozole

These patients were treated with letrozole (Femara®, Novartis New York, NY, USA) in a dose 2.5 mg (one tablet daily) orally began on the 3rd day to the 7th day of the cycle. If ovulation is not achieved dose is increased by 2.5 mg in next cycle till 3 cycles.

Group Type EXPERIMENTAL

Letrozole 2.5mg

Intervention Type DRUG

These patients were treated with letrozole (Femara®, Novartis New York, NY, USA) in a dose 2.5 mg (one tablet daily) orally began on the 3rd day to the 7th day of the cycle. If ovulation is not achieved dose is increased by 2.5 mg in next cycle till 3 cycles

Gonadotropins

These patients were given urofollitropin (fostimon ®, IBSA, Lugano, Switzerland) in a dose of 75 IU/mL I.M from day 3rd to day 7th of the cycle beginning by one ampoule per day and the dose had been modulated according to response.

Group Type ACTIVE_COMPARATOR

Gonadotropin

Intervention Type DRUG

These patients were given urofollitropin (fostimon ®, IBSA, Lugano, Switzerland) in a dose of 75 IU/mL I.M from day 3rd to day 7th of the cycle beginning by one ampoule per day and the dose had been modulated according to response.

Interventions

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Letrozole 2.5mg

These patients were treated with letrozole (Femara®, Novartis New York, NY, USA) in a dose 2.5 mg (one tablet daily) orally began on the 3rd day to the 7th day of the cycle. If ovulation is not achieved dose is increased by 2.5 mg in next cycle till 3 cycles

Intervention Type DRUG

Gonadotropin

These patients were given urofollitropin (fostimon ®, IBSA, Lugano, Switzerland) in a dose of 75 IU/mL I.M from day 3rd to day 7th of the cycle beginning by one ampoule per day and the dose had been modulated according to response.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Infertility lasting one year or more in presence of regular intercourse,
* Patients' age between 20-35years
* Normal semen analysis according to WHO 2010
* Patent fallopian tubes (e) Normal prolactin and TSH.
* Anovulatory cycles confirmed by mid-luteal progesterone ≤ 3 ng/ml and
* Clomiphene citrate resistance for 3 cycles of 150mg.

Exclusion Criteria

* Any hormonal disturbances eg. hyperprolactinemia,
* Immunological causes of infertility,
* Coital errors,
* Metabolic disorders and
* Poor patient compliance.
Minimum Eligible Age

20 Years

Maximum Eligible Age

35 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Tanta University

OTHER

Sponsor Role lead

Responsible Party

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Ayman S Dawood, MD

Assistant professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ayman Dawood, MD

Role: PRINCIPAL_INVESTIGATOR

Assistant professor

Locations

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Ayman Shehata Dawood

Tanta, Gharbia Governorate, Egypt

Site Status

Countries

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Egypt

Other Identifiers

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CCR

Identifier Type: -

Identifier Source: org_study_id

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