BMI Effect on the Response to Ovulation Induction in Letrozole vs Clomid

Effect of High BMI on Ovulation Induction Using Letrozole Versus Clomid

There is an increased prevalence of high Body mass index (BMI) all over the world.High BMI is shown to have an impact on the female reproductive system.It can contribute to both ovulatory and anovulatory subfertility.

Clomiphene citrate and Letrozole have been used for treatment of infertility.Both are used for induction of ovulation.

Clomiphene citrate is an estrogen receptor antagonist .It increases serum FSH and it has its limitation due to his antiestrogenic effect,it has an ovulation rate 70-80% but pregnancy rate is only 22% because of its anti-estrogenic effect on endometrium and poor cervical mucus (Legro RS et al.,2007) Letrozole is an aromatase inhibitor which inhibits the production of estrogen, which influences the action of the brain's hypothalamus and pituitary on the functioning of the ovaries by increasing FSH.Due to the antiestrogenic effect of clomiphene citrate,Letrozole can be used as an alternative.

The investigators are comparing the effect of both medications on the outcome of the induction of ovulation in women with high BMI.

Study Overview

• Status: Unknown
• Conditions: Subfertility
• Intervention / Treatment: Drug: Clomiphene Citrate 50mg; Drug: Letrozole 2.5mg

Detailed Description

This is a Randomized controlled trial .The researchers include160 women with BMI more than 30 who were suffering from subfertility for more than 2 years. The investigators will randomise them into 2 groups. Group A:They were prescribed 100 mg of clomiphene citrate from day 2-5 of the cycle for 5 days. Group B : They were prescribed 5 mg of Letrozole from day 2-5 of the cycle.

Vaginal ultrasound was performed on day 11 of the cycle, After at least one follicle reached 15 mm, The patient was encouraged to have sexual intercourse every other day for few days.The patients will have a midluteal progesterone level to confirm ovulation and will have a pregnancy test in 2 weeks if missed period. The researchers will compare the number of mature follicles, endometrial thickness on the day when there are mature follicles, occurrence of pregnancy, multiple pregnancies, and miscarriages .

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Eman Elkattan, MD,MRCOG,DFSRH; Phone Number: 01212529213; Email: emyelkattan@gmail.com
• Study Contact Backup: Name: Amira Saeed, MD; Email: amirasaied2026@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age: 18-45 years old.
• History of subfertility for 2 years.
• No previous IVF
• Intact tubes as evidenced by HSG or Hycosy
• Normal Sperm parameters according to WHO criteria.
• Ability to have regular intercourse during the ovulation induction phase of the study.

Exclusion Criteria:

• Age less than 18 years old or older than 45 years old.
• FSH> 15 mIU/ml
• Tubal factor of infertility
• Male factor of infertility
• Current pregnancy,abnormal uterine bleeding.
• History of use of hormonal contraception in the last 3 months.
• Untreated medical problems: thyroid disease,hyperprolactinemia or contraindication to pregnancy as uncontrolled diabetes or severe heart disease.
• Contraindications to clomiphene citrate: hypersensitivity to clomid.
• Contraindications to letrozole: hypersensitivity to letrozole .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clomiphene Citrate-High BMI women; Clomid 50 mg, 2 tablets orally every day from day 2-5 of the period for 5 days	Drug: Clomiphene Citrate 50mg; Clomid 50 mg, 2 tablets orally every day from day 2-5 of the period for 5 days; Other Names: Clomid
Active Comparator: Letrozole-High BMI women; Femara 2.5 mg, 2 tablets orally every day from day 2-5 of the period for 5 days	Drug: Letrozole 2.5mg; Femara 2.5 mg, 2 tablets orally every day from day 2-5 of the period for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evidence of ovulation	Raised concentration of serum progesterone	day 21 of 28 day cycle or 7 days post LH surge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of mature follicles	Number of follicles> 15mm	day 12-19 of the cycle (At the end of the treatment cycles, each cycle 28 days)
Endometrial thickness	the thickest part of the endometrial lining at the longitudinal plane at the time of mature follicle	day 12-19 of the cycle (At the end of the treatment cycles, each cycle 28 days)
Conception	Number of participants with positive pregnancy test (serum or urine),serum BHCG > 25 IU/L	4-5 weeks post treatment
clinical pregnancy	Number of participants with gestational sac with positive fatal pulsation	6 weeks post treatment

Collaborators and Investigators

• Sponsor: Cairo University

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2020
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: March 27, 2020
• First Submitted That Met QC Criteria: March 31, 2020
• First Posted (Actual): April 2, 2020

Study Record Updates

• Last Update Posted (Actual): April 2, 2020
• Last Update Submitted That Met QC Criteria: March 31, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Clomiphene; Enclomiphene; Zuclomiphene
• Other Study ID Numbers: Protocol 600

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No