A Comparison of Letrozole and Clomifene Citrate

Not Applicable

• Conditions: Subfertility; Polycystic Ovarian Syndrome
• Interventions: Drug: Letrozole; Drug: Clomiphene

• Registration Number: NCT02647424
• Lead Sponsor: The University of Hong Kong

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-12
• Study First Submitted: 2015-12-29
• Study First Submitted QC: 2016-01-05
• Study First Posted: 2016-01-06
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-26
• Last Update Posted: 2016-10-27
• Primary Completion: 2017-12
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PCOS group	Letrozole	PCOS women with anovulation
Ovulatory group	Letrozole	Ovulatory group planned for intra-uterine insemination
PCOS group	Clomiphene	PCOS women with anovulation
Ovulatory group	Clomiphene	Ovulatory group planned for intra-uterine insemination

Primary Outcome Measures

Name	Time	Method
FSH concentrations	Alternative day during ovulation induction cycle (for about 3 month)

Secondary Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (1)

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong