A Comparison of Letrozole and Clomifene Citrate

Study Overview
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Brief Summary
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Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies, affecting 5% to 10% of women of reproductive age. Women with PCOS suffer from anovulatory infertility. Following lifestyle modification with weight reduction in obese PCOS women, clomifene citrate (CC) is considered the first line treatment for ovulation induction (OI) in these women. 75-80% of women will ovulate after CC administration. However, there is a discrepancy between the ovulation rate and pregnancy rate, which was reported to be 22% per each ovulating cycles after CC. Other alternatives, including gonadotropin injections and laparoscopic ovarian drilling, carried different disadvantages, such as costly treatment and risks of ovarian hyperstimulation syndrome and multiple pregnancy rate in gonadotrophin therapy and surgical risks and risk of ovarian failure in surgical treatment. The use of aromatase inhibitor, letrozole (LTZ), in reproductive medicine started in 2001. After this publication, there have been many groups of investigators studying the use of LTZ either in OI or ovarian stimulation in IVF cycles. A large multicentre randomized trial reported a significantly higher ovulation rate and live-birth rate comparing LTZ with CC. In majority of the publications, the multiple pregnancy rate was lower in LTZ group than in CC group. This can be attributed to the higher chance of monofollicular development after LTZ compared with CC. However, there is no information comparing the hormonal profile and follicular development after letrozole and CC. Mild ovarian stimulation using LTZ or CC in conjunction with intrauterine insemination is commonly offered to ovulatory women with unexplained infertility, minimal endometriosis or mild factor to improve the pregnancy rate. There is again no information comparing the hormonal profile and follicular development after letrozole and CC in ovulatory women. The aim of this study is to compare the hormonal profile after the use of LTZ and CC in anovulatory PCOS women and ovulatory women with unexplained subfertility. The hypothesis is that the FSH risk after LTZ is shorter than that of CC.

Detailed Description
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Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies, affecting 5% to 10% of women of reproductive age. Women with PCOS suffer from anovulatory infertility. Following lifestyle modification with weight reduction in obese PCOS women, clomifene citrate (CC) is considered the first line treatment for ovulation induction (OI) in these women. 75-80% of women will ovulate after CC administration. However, there is a discrepancy between the ovulation rate and pregnancy rate, which was reported to be 22% per each ovulating cycles after CC. Other alternatives, including gonadotropin injections and laparoscopic ovarian drilling, carried different disadvantages, such as costly treatment and risks of ovarian hyperstimulation syndrome and multiple pregnancy rate in gonadotrophin therapy and surgical risks and risk of ovarian failure in surgical treatment. The use of aromatase inhibitor, letrozole (LTZ), in reproductive medicine started in 2001. After this publication, there have been many groups of investigators studying the use of LTZ either in OI or ovarian stimulation in IVF cycles. A large multicentre randomized trial reported a significantly higher ovulation rate and live-birth rate comparing LTZ with CC. In majority of the publications, the multiple pregnancy rate was lower in LTZ group than in CC group. This can be attributed to the higher chance of monofollicular development after LTZ compared with CC. However, there is no information comparing the hormonal profile and follicular development after letrozole and CC. Mild ovarian stimulation using LTZ or CC in conjunction with intrauterine insemination is commonly offered to ovulatory women with unexplained infertility, minimal endometriosis or mild factor to improve the pregnancy rate. There is again no information comparing the hormonal profile and follicular development after letrozole and CC in ovulatory women. The aim of this study is to compare the hormonal profile after the use of LTZ and CC in anovulatory PCOS women and ovulatory women with unexplained subfertility. The hypothesis is that the FSH risk after LTZ is shorter than that of CC.

Official Title
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A Comparison of Hormonal Profile and the Follicular Development Between Letrozole and Clomifene Citrate in Anovulatory Women With Polycystic Ovary Syndrome and Ovulatory Women

Conditions
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Polycystic Ovarian Syndrome, Subfertility

Intervention / Treatment
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* Drug: Letrozole
* Drug: Clomiphene


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age of women 18-39 years Irregular menstrual cycles with anovulation (cycle >35 days) together with polycystic ovaries on pelvic scanning or laboratory/clinical hyperandrogenism (in PCOS group) Regular cycle of 25-35 days cycle for the ovulatory women group Body mass index </= 30 kg/m2 Exclusion criteria: Couples undergoing ART treatment cycles History of ovarian surgery Drug allergy to CC or LTZ History of diabetes mellitus or other severe medical diseases Refusal to join the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: PCOS group<br>PCOS women with anovulation | Drug: Letrozole<br>* Letrozole 2.5 mg daily from Day 2 to 6<br>* Other names: Letrozole group;Drug: Clomiphene<br>* After one month of washout period, clomiphene 50 mg daily from day 2 to day 6 given<br>* Other names: Clomiphene group;|
| Other: Ovulatory group<br>Ovulatory group planned for intra-uterine insemination | Drug: Letrozole<br>* Letrozole 2.5 mg daily from Day 2 to 6<br>* Other names: Letrozole group;Drug: Clomiphene<br>* After one month of washout period, clomiphene 50 mg daily from day 2 to day 6 given<br>* Other names: Clomiphene group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FSH concentrations |  | Alternative day during ovulation induction cycle (for about 3 month) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LHconcentration |  | Alternative day during ovulation induction cycles (for about 3 month) | 
| Endometrial Thickness |  | Monitoring during ovulation induction cycle (for about 3 month) | 
| Oestradiol concentration |  | Alternative day during ovulation induction cycles (for about 3 month) | 
| Progesterone concentration |  | Alternative day during ovulation induction cycles (for about 3 month) | 
| Number of growing follicles |  | Monitoring during OI cycles (for about 3 month) |