A Comparison of Letrozole and Clomifene Citrate

Polycystic Ovarian Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02647424
• Other study ID #: HKU-VL-LCC
• Status: Recruiting
• Phase: N/A
• First received: December 29, 2015
• Last updated: October 26, 2016
• Start date: December 2015
• Est. completion date: December 2017

Study information

• Verified date: October 2016
• Source: The University of Hong Kong
• Contact: Vivian Lee, MBBS, MRCOG
• Phone: 22553400
• Email: v200lee[@]hku.hk
• Is FDA regulated: No
• Health authority: Hong Kong: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 39 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility
• Polycystic Ovarian Syndrome
• Polycystic Ovary Syndrome
• Subfertility
• Syndrome

Intervention

Drug:
• Letrozole
Letrozole 2.5 mg daily from Day 2 to 6
• Clomiphene
After one month of washout period, clomiphene 50 mg daily from day 2 to day 6 given

Locations

Country	Name	City	State
Hong Kong	Queen Mary Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FSH concentrations		Alternative day during ovulation induction cycle (for about 3 month)	No
Secondary	LHconcentration		Alternative day during ovulation induction cycles (for about 3 month)	No
Secondary	Endometrial Thickness		Monitoring during ovulation induction cycle (for about 3 month)	No
Secondary	Oestradiol concentration		Alternative day during ovulation induction cycles (for about 3 month)	No
Secondary	Progesterone concentration		Alternative day during ovulation induction cycles (for about 3 month)	No
Secondary	Number of growing follicles		Monitoring during OI cycles (for about 3 month)	No