The Effect of Tamoxifen on Clinical Outcome in Women With Thin Endometrium Undergoing Frozen Thawed Cycle.

The Effect of Tamoxifen on Endometrial Thickness and Pregnancy Outcome in Women With Thin Endometrium Undergoing Frozen Thawed Cycle.

Cryopreservation of embryos created during fresh IVF cycles provides a less expensive and time-intensive opportunity for pregnancy. Ideal endometrium thickness is the key point to optimization FET cycle. Researches show that when endometrial thickness is less than 7mm, pregnancy rate dropped significantly. Tamoxifen has been reported to be oestrogenic on the lower genital tract. Several study on intrauterine insemination or ovulation induction suggest that tamoxifen may be a promising alternative for patients with thin endometrium. Based on this ,we want to evaluate the effects of tamoxifen on endometrial thickness and pregnancy outcome in women who failed to develop an adequate endometrial thickness in previous frozen embryo transfer cycle twice or even more times and willing to have another attempt.

Study Overview

• Status: Unknown
• Conditions: Endometrium
• Intervention / Treatment: Drug: Tamoxifen; Drug: estradiol valerate

Detailed Description

Objective: To investigate the effects of tamoxifen on endometrial thickness and pregnancy outcome in women with thin endometrium undergoing frozen thawed cycle.

Study design: This is a single center, randomize control clinical trial. We plan to recruit 100 patients from Mar 2017 to Dec 2019, who failed to develop an adequate endometrial thickness in previous frozen embryo transfer cycle twice or even more times and willing to have another attempt, dividing into two group, one prepare the endometrium through ovulation induction with tamoxifen and progesterone(Study Group), the other is hormone replacement cycle (control group).

Intervention: Study Group will give endometrial preparation with tamoxifen and progesterone, control group will prepared with estrogen and progesterone supplementation.

Main outcome measures: The primary outcome of the study was endometrium thickness and clinical pregnancy rate, the secondary outcomes are cycle duration, cycle cancellation rate, implantation rate, miscarriage rate, live birth rate.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xing Yang, M.D. & Ph.D.; Phone Number: 020-38048013; Email: yxing_8358@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women age ≥20 years and ≤40 years;
2. patients that have at least 1 high quality blastocysts;
3. patients who are observed endometrial thickness ≤ 7mm in the past natural cycles or hormone replacement cycles repeatedly (twice or even more);
4. patients intends to continue to attempt another frozen embryo transfer cycle.

Exclusion Criteria:

1. patients diagnosed intrauterine adhesions, uterine scarring diverticulum via Hysteroscopy or ultrasonography and have history of uterine cavity operation for the above indication;
2. patients have congenital uterine anomalies such as Gemini, the mediastinum in the uterus and so on.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: study group; Patients in study group will receive tamoxifen at a daily dose of 40 mg from day 3 to day 8. Follicle diameters are monitored by transvaginal ultrasound and serum levels of E2, P are tested on day 9. If there is a dominant follicle (almost 12 × 12 mm in diameter), endometrial thickness and endometrial pattern, as well as follicular diameters, were monitored daily or every other day till embryo transfer. Serum levels of E2, P are tested on the day before ovulation. If there isn't dominant follicle and intramuscular human menopausal gonadotropin at a dose of 75-150 IU was administered each day after day 12 if there follicle development was poor. The embryo transfer day is decided according embryo development.	Drug: Tamoxifen; Patients in study group will receive tamoxifen at a daily dose of 40 mg from day 3 to day 8.; Other Names: Tam
Active Comparator: control group; Patients in control group will receive estradiol valerate at a dose of 3 mg twice per day from day 3. Follicle diameters are monitored by transvaginal ultrasound and serum levels of E2, P are tested on day 9. If endometrial thickness <7mm and E2<100pg/ml, the dose of estradiol valerate can increase or combine other estradiol. Endometrial thickness and endometrial pattern, as well as follicular diameters, were monitored daily or every other day till embryo transfer. Serum levels of E2, P are tested on the day before endometrium transformation. The embryo transfer day is decided according embryo development. Serum levels of E2, P are tested on the day before embryo transfer.	Drug: estradiol valerate; Patients in control group will receive estradiol valerate at a dose of 3 mg twice per day from day 3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
endometrium thickness	Endometrial thickness was defined as the maximal distance between the echogenic interfaces of the endometrium and the myometrium in the plane of the central longitudinal axis of the uterus.	1-3 month
clinical pregnancy rate	Clinical pregnancy was considered with the presence of a gestational sac containing yolk sac at transvaginal ultrasonography, including ectopic pregnancy.clinical pregnancy rate is the number of clinical pregnancy patients /the total number of transferred patients in the group.	1-2years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cycle duration	the total time of endometrium preparation	1-3 month
cycle cancellation rate	cycle cancellation rate is the number of patients that cancell embryo transfer /the total number of patients in the group.	1-3 month
implantation rate	Implantation rate was determined by the number of gestational sacs and the total number of embryos transferred at least 4 weeks after embryo transfer.	1-2 year
miscarriage rate	miscarriage rate is the number of patients that find pregnancy loss /the total number of transferred patients in the group.	1-2 year
live birth rate	live birth rate is the number of patients that delived /the total number of transferred patients in the group.	1-2 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Director: Xing Yang, M.D. & Ph.D., The Sixth Affiliated Hospital,Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2017
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): June 1, 2020

Study Registration Dates

• First Submitted: February 18, 2017
• First Submitted That Met QC Criteria: February 18, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): February 24, 2017
• Last Update Submitted That Met QC Criteria: February 22, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: tamoxifen; pregnancy rate; thin endometrium; frozen embryo transfer
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Estrogens; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Estradiol; Tamoxifen; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: newivf20170217

Drug and device information, study documents

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