Clinical trial NCT02458404: Effects of Varied Estrogen Doses on Endometrial Receptivity
Official title: Effects of Varied Estrogen Doses on Endometrial Receptivity
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Luteal Phase Defect
Lead sponsor: Reproductive Medicine Associates of New Jersey
Sponsor class: OTHER
First posted: 2015-06-01
Enrollment: 19
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy human subjects

Brief summary: This study will help determine the effect of varied estradiol levels on the uterine lining in healthy humans that are not undergoing a stimulated in vitro fertilization (IVF) cycle.

Detailed description: Volunteers who wish to participate in the study, will undergo a diagnostic and screening phase to determine their eligibility. Once eligibility is determined, participants will undergo three, separate "endometrial preparatory cycles". These cycles will consist of estrogen supplementation to mimic normal, above normal, and highly elevated estradiol levels. Once supplementation is complete uterine procedures will be done to hopefully determine the effects of the estrogen levels on the uterine lining. Subcutaneous leuprolide injections, intramuscular estrogen, and progesterone injections will be used to mimic the levels needed. Blood draws will monitor the needed estradiol and progesterone levels during the injection phase of the cycle. Once the injection phase is complete, transvaginal ultrasound, uterine aspiration, and endometrial biopsy will be done.

Eligibility criteria: Inclusion Criteria:

* Regular menstrual cycles
* Age 18-50
* Normal Baseline ultrasound
* No intra-uterine procedures in prior 90 days

Exclusion Criteria:

* Any contraindications to undergoing estrogen stimulation of the endometrium
* Age ≥35 years and smoking ≥15 cigarettes per day
* Multiple risk factors for arterial cardiovascular disease (smoking, diabetes, and hypertension)
* Hypertension (systolic ≥140 mmHg or diastolic ≥90 mmHg)
* Venous thromboembolism (current or history of)
* Known thrombogenic mutations
* Known ischemic heart disease
* History of stroke
* Complicated valvular heart disease (pulmonary hypertension, risk for atrial fibrillation, history of subacute bacterial endocarditis)
* Systemic lupus erythematosus (positive or unknown antiphospholipid antibodies)
* Migraine with aura at any age
* Breast cancer
* Cirrhosis
* Hepatocellular adenoma or malignant hepatoma
* History of undiagnosed abnormal uterine bleeding.
* Allergic reaction to any study drug
* Known pregnancy or delivery within the past 6 months
* Breastfeeding
* Obesity \>35 kg/m2

Primary outcomes:
measure: Endometrial thickness in millimeters as assessed by transvaginal ultrasound
timeFrame: Participants will be followed for the duration of 1 menstrual cycle, ~30 days; this is followed by 1 rest mentrual cycle, ~30 days; there are a total of 3 rest and 3 treatment cycles, ~180 days
measure: mRNA and protein expression of known markers of secretory transformation as assessed by real time PCR and immunohistochemistry after uterine aspiration and disruption/biops
timeFrame: Participants will be followed for the duration of 1 menstrual cycle, ~30 days; this is followed by 1 rest mentrual cycle, ~30 days; there are a total of 3 rest and 3 treatment cycles, ~180 days
measure: Endometrial echotexture as assessed by transvaginal ultrasound
timeFrame: Participants will be followed for the duration of 1 menstrual cycle, ~30 days; this is followed by 1 rest mentrual cycle, ~30 days; there are a total of 3 rest and 3 treatment cycles, ~180 days
Secondary outcomes:
measure: Peak and trough estrogen and progesterone levels as assessed by peripheral phlebotomy
timeFrame: Participants will be followed for the duration of 1 menstrual cycle, ~30 days; this is followed by 1 rest mentrual cycle, ~30 days; there are a total of 3 rest and 3 treatment cycles, ~180 days
measure: Uterine microbiome characterization by microbiota presence and prevalence as assessed after uterine aspiration
timeFrame: Participants will be followed for the duration of 1 menstrual cycle, ~30 days; this is followed by 1 rest mentrual cycle, ~30 days; there are a total of 3 rest and 3 treatment cycles, ~180 days
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Reproductive Medicine Associates of New Jersey
state: New Jersey
Study officials:
affiliation: RMA of NJ
name: Richard T Scott, MD, HCLD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Osman EK, Wang T, Zhan Y, Juneau CR, Morin SJ, Seli E, Scott RT, Franasiak JM. Varying levels of serum estradiol do not alter the timing of the early endometrial secretory transformation. Hum Reprod. 2020 Jul 1;35(7):1637-1647. doi: 10.1093/humrep/deaa135.