Effects of Clomiphene Citrate Ovulation Induction on Frozen Embryo Transfer

Clomiphene citrate has been widely used for treatment of infertility for decades. Although its anti-estrogenic effects leads to low pregnancy rate, clomiphene citrate is still a first-line treatment for ovulation induction because of its simple usage, low prices, no injection and low risk of ovarian hyperstimulation syndrome. Clomiphene citrate shows high affinity with estrogen receptor, which inhibits endometrial proliferation, inevitably leads to a decline in endometrial receptivity, thus affecting the success rate of IVF.

In that case, use clomiphene citrate for ovulation induction is lost more than gained based on fresh embryo transfer. But recently, some researchers have proposed to extend the time from ovulation induction to embryo transfer, and the increased level of estradiol can replace clomiphene citrate to combine with the receptor, so that the uterine environment is more conducive to pregnancy. Therefore, use clomiphene citrate based on vitrification of embryo maybe a good way for treatment of infertility.

At present, using frozen embryo transplantation after ovulation induction by clomiphene citrate is a common treatment, but few research has mentioned the best time for embryo implantation. The investigators research is to find the most appropriate time for frozen embryo implantation after using clomiphene citrate for ovulation induction.

Study Overview

• Status: Unknown
• Conditions: Infertility, Female; Clomiphene Citrate
• Intervention / Treatment: Drug: Clomiphene Citrate protocol; Procedure: Procedure

Detailed Description

This study receives patients from 2017 August to 2018 June who undergo ART treatment at Shanghai Jiai Genetics & IVF Institute and taken either CC or GnRH antagonist protocol(control group) for ovulation induction.

The investigators will record every patients' age, BMI, serum E2, P, LH level, infertility factors and pregnancy outcomes, counted the implantation rate and clinical pregnancy rate, and then used SPSS Software x2 test for statistical analysis, the significance was set at p<0.05.The investigators will also make a correlation analysis about the serum hormone level and pregnancy outcomes.

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: YINING XU, MD; Phone Number: 86-13564548586; Email: 10301010067@fudan.edu.cn

Study Locations

• China
  • Shanghai, China, 200011
    • Recruiting
    • Shanghai JiAi Genetics & IVF Institute
    • Contact: XIAOXI SUN, MD; Phone Number: 86-21-63456043; Email: steven3019@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Women 18-40 years of age who are scheduled for IVF or ICSI in our IVF institute while meeting the following criteria:

1. AMH ≥ 2;
2. Infertility factors: tubal factor, severe oligospermia, etc;
3. FET cycle;
4. Cleavage stage embryo transfer (Day 3).

Exclusion Criteria:

1. BMI ≤ 18.4 or ≥ 25.0;
2. Have pregnancy complications;
3. Genital tract malformations, uterine cavity diseases, PCOS;
4. Endometriosis;
5. Genetic diseases, severe somatic diseases, mental disorder.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Use Clomiphene Citrate protocol; Ovulation induction: regular Clomiphene Citrate protocol. Start use rFSH or HMG from day 2/3 of the menstrual cycle, the initial dosage is determined by patients' age, BMI, antral follicle number, FSH, E2, AMH and past ovarian response, usually 150-225IU/d, until hCG injection. At the same time, take CC 100mg/d until hCG injection. The dosage of Gn will be adjust by serum E2, P, LH and the development of follicular.	Drug: Clomiphene Citrate protocol; Take CC 100mg/d at the same time with Gn until hCG injection.; Other Names: CC
Active Comparator: Procedure; Ovulation induction: regular GnRH antagonist protocol. Start use rFSH or HMG from day 2/3 of the menstrual cycle, the initial dosage is determined by patients' age, BMI, antral follicle number, FSH, E2, AMH and past ovarian response, usually 150-225IU/d, until hCG injection. When a dominant follicle diameter over 14mm or serum E2 over 350pg/ml, use GnRH-ant 0.25mg/d, until hCG injection. The dosage of Gn will be adjust by serum E2, P, LH and the development of follicular.	Procedure: Procedure; When a dominant follicle diameter over 14mm or serum E2 over 350pg/ml, use GnRH-ant 0.25mg/d, until hCG injection.; Other Names: GnRH antagonist protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy	Clinical pregnancy is defined as the presence of a gestational sac confirmed by transvaginal ultrasound examination. Clinical pregnancy rate per treatment cycle will also be calculated based on ITT.	4 weeks after embryo transfer for the patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ongoing pregnancy	Ongoing pregnancy is defined as a viable intrauterine pregnancy after 12 weeks of embryo transfer. Ongoing pregnancy rate per treatment cycle will also be calculated on intend-to-treat(ITT) basis.	12 weeks after embryo transfer for the patient
Implantation of transferred embryo	Implantation rate per embryo transferred will also be calculated.	2 weeks after embryo transfer for the patient

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regression analysis 1	Regression analysis about the pregnancy outcomes and patients' serum E2,P4,LH levels on the day of hCG injection	12 weeks after embryo transfer for the patient
Regression analysis 2	Regression analysis about the pregnancy outcomes and patients' serum E2,P4,LH levels on the day of embryo transfer	12 weeks after embryo transfer for the patient

Collaborators and Investigators

• Sponsor: ShangHai Ji Ai Genetics & IVF Institute
• Investigators: Study Chair: XIAOXI SUN, MD, Shanghai JiAi Genetics & IVF Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2017
• Primary Completion (Anticipated): June 30, 2018
• Study Completion (Anticipated): June 30, 2018

Study Registration Dates

• First Submitted: February 28, 2017
• First Submitted That Met QC Criteria: October 7, 2017
• First Posted (Actual): October 13, 2017

Study Record Updates

• Last Update Posted (Actual): October 13, 2017
• Last Update Submitted That Met QC Criteria: October 7, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Infertility, Female; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Clomiphene; Enclomiphene; Zuclomiphene
• Other Study ID Numbers: JIAI E2017-11

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No