Effect of Testosterone Pretreatment in POR

Therapeutic Effect of Prolonged Testosterone Pretreatment in Women With Poor Ovarian Response: a Randomized Control Trial

This study compared the therapeutic effect of 4- and 6-week TTG application before controlled ovarian hyperstimulation (COH) in POR.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: Testosterone gel

Detailed Description

This randomized control trial (RCT) was conducted between January 2018 and September 2019 at the National Center for Reproductive Medicine, Hanoi, Vietnam. The eligibility of a total of 165 women with POR, undergoing IVF treatment, to be enrolled in the study was assessed. Inclusion criteria included patients who met at least two of the following criteria: (i) having one previous IVF/ intracytoplasmic sperm injection (ICSI) cycle with ≤ 3 oocytes recruited; (ii) AFC ≤ 5-7; and (iii) anti-Mullerian hormone (AMH) ≤ 0.5 - 1.1 ng/mL were enrolled. Exclusion criteria included donated gamete IVF cycles, thyroid disease, liver and kidney dysfunction, and abnormal genitalia. After screening, eligible patients were randomly allocated into two TTG intervention groups (4-week and 6-week groups) and one control group through a manual lottery. Allocation concealment was by sequentially numbered, opaque, sealed envelopes. All participants were blinded to group assignment, but researchers were not blinded.

Serum testosterone are measured before treatment. Durations of androgen supplement are 4 or 6-weeks. After completing the pretreatment, patients are asked to come back when they have menses to begin IVF treatment. Serum testosterone is measured again after the pretreatment in both groups. Patients will be interviewed for side effects and compliance of treatment.

After treatment, patients in both group undergo IVF treatment. IVF treatment will then be performed for all patients, according to the current hospital treatment protocols.

Patients will be followed up at least until 12th week of gestation, if they have positive pregnancy test after embryo transfer.

Data were analyzed using STATA software version 14.0 (Stata Corporation, College Station, TX, USA). Data were analyzed on an intention-to-treat basis. Proportions, means, and standard deviations (SDs) were examined and presented for selected baseline variables by treatment group. Comparisons of baseline characteristics and outcomes by treatment group were performed with the use of ANOVA for continuous variables and a chi-square test for proportions. A Bonferroni correction was used for multiple testing, in which the resulting P-value was multiplied by the number of tests that measured similar constructs. Multivariable logistic regressions were used to quantify the effects of the treatment group, adjusted for all potential confounders including maternal age, body mass index (BMI), infertility duration, primary or secondary infertility, and history of IVF treatment. All statistical tests were two-sided, and P values < 0.05 were considered statistically significant.

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Vietnam
  • Hanoi, Vietnam, 250000
    • Hanoi Medical University, Vietnam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 47 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria: patients who met at least two of the following criteria

• Having one previous IVF/ intracytoplasmic sperm injection (ICSI) cycle with ≤ 3 oocytes recruited.
• AFC ≤ 5 - 7.
• Anti-Mullerian hormone (AMH) ≤ 0.5 - 1.1 ng/mL.

Exclusion Criteria:

• donated gamete IVF cycles
• Thyroid disease
• Liver and kidney dysfunction
• Abnormal genitalia

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Testosterone gel 4 weeks; Patients with low ovarian reserve received 4-week TTG application before controlled ovarian hyperstimulation.	Drug: Testosterone gel; Apply 12.5mg testosterone gel to the abdomen and rub on with one finger, once a day, in the morning, then allow sites to dry and cover with clothing. Continue the treatment for 4 or 6 weeks until next IVF treatment.; Other Names: Androgel 1% Transdermal Gel
Experimental: Testosterone gel 6 weeks; Patients with low ovarian reserve received 6-week TTG application before controlled ovarian hyperstimulation.	Drug: Testosterone gel; Apply 12.5mg testosterone gel to the abdomen and rub on with one finger, once a day, in the morning, then allow sites to dry and cover with clothing. Continue the treatment for 4 or 6 weeks until next IVF treatment.; Other Names: Androgel 1% Transdermal Gel
No Intervention: Control group; Patients with low ovarian reserve received no medication before controlled ovarian hyperstimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of oocytes retrieved	The main outcomes of our study were the total number of retrieved	30 minutes after oocyte retrieval complete

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy rates.	Pregnancy was defined as positive when the serum beta-hCG level was ≥ 50 IU/L	14 days after embryo transfer
clinical pregnancy rates.	Clinical pregnancy was defined as the presence of a gestational sac identified by transvaginal ultrasound	4 weeks after embryo transfer
Ongoing pregnancy rates	Ongoing pregnancy was defined as a viable intrauterine pregnancy after 12 weeks of gestation.	after 12 weeks of gestation

Collaborators and Investigators

• Sponsor: Hanoi Medical University
• Collaborators: National Hospital of Obstetrics and Gynecology
• Investigators: Study Director: Hung S Ho, MD, PhD, Hanoi Medical University, Vietnam; Study Chair: Tien V Nguyen, MD, PhD, Hanoi Medical University, Vietnam

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2018
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: October 20, 2020
• First Submitted That Met QC Criteria: October 20, 2020
• First Posted (Actual): October 26, 2020

Study Record Updates

• Last Update Posted (Actual): October 26, 2020
• Last Update Submitted That Met QC Criteria: October 20, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: hoangquochuy, MD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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