Obesity, Fertility
Conditions
Keywords
obesity, fertility, infertility, reproductive hormones
Brief summary
Excess maternal weight, especially obesity, influences almost every aspect of fertility, from conception to problems during pregnancy. The investigators will use novel statistical methods to clarify the hormonal changes behind reproductive health conditions. A better understanding of reproductive hormonal changes in obese women may offer a way to identify new treatments.
Detailed description
Hypothesis. Insufficient FSH (Follicle-stimulating hormone) pulsatility, as seen in obesity, results in inadequate folliculogenesis and reduced ovarian steroid and protein production. AIM: To test the hypothesis that insufficient FSH pulsatility, as seen in obesity, results in inadequate folliculogenesis and reduced ovarian steroid and protein production. The investigators will determine if exogenous FSH administered in a pulsatile fashion results in a significant increase of ovarian hormones in obese women. Serial inhibin B and E2 levels will be measured in obese and normal weight women undergoing frequent blood sampling studies before and after GnRH (Gonadotropin-releasing hormone) antagonist blockade.
Interventions
DRUGDegarelix (GnRH antagonist)
Day-1: Blood samples will be obtained every 10 minutes for 10 hours. After 10 hours of blood samples have been collected, the GnRH antagonist degarelix will be given subcutaneously.
DRUGrecombinant FSH
Day-2: Blood samples will again be obtained every 10 minutes for 10 hours. Repeated boluses of exogenous recombinant FSH (rFSH) will be given by IV during this 10 hour visit.
DRUGCetrorelix
Day-1: Blood samples will be obtained every 10 minutes for 10 hours. After 10 hours of blood samples have been collected, the GnRH antagonist Cetrorelix will be given subcutaneously.
Sponsors
University of Colorado, Denver
National Center for Advancing Translational Sciences (NCATS)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 39 Years
Healthy volunteers
Yes
Inclusion criteria
* Age between 21 to 39 years old with regular menstrual cycles every 25-40 days * Body mass of 18.5 kg/m2-24.9kg/m2 (normal weight controls) or greater than 30.0 kg/m2 (obese group) * Prolactin and thyroid-stimulating hormone (TSH) within normal laboratory ranges at screening * Baseline hemoglobin \>11 gm/dl.
Exclusion criteria
* Diagnosis of polycystic ovary syndrome (PCOS), defined by the 2003 Rotterdam criteria as suggested by 2012 NIH Workshop * History of chronic disease affecting hormone production, metabolism or clearance or use of thiazolidinediones or metformin (known to interact with reproductive hormones) * Use of hormones affecting hypothalamic-pituitary-gonadal (HPO) axis (such as hormonal contraceptives) within 3 months of entry * Strenuous exercise (\>4 hours of intense physical activity per week) * Pregnancy * Breast-feeding * Current attempts to conceive * Significant recent weight loss or gain
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between Peak Inhibin B | Every 10 minutes over 2 10-hour frequent blood sampling sessions. | This is defined as the maximum hormone value during Day 1 of the study subtracted from the maximum hormone value during Day 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Inhibin B Per Subject | Every 10 minutes over 10 hours on Day 1 and Day 2 of the study. | Peak inhibin B will be measured every 10 minutes during day 1 and day 2 of the study. The highest inhibin B value will be defined as the peak. |
| Peak E2 Per Subject | Every 10 minutes over 10 hours of Day 1 and Day 2 of the study. | E2 will be measured every 10 minutes on Day 1 and Day 2 of the study. The highest E2 value will be designated as the peak E2 value. |
Countries
United States
Participant flow
Pre-assignment details
Some participants were excluded after signing the consent.
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Frequent Blood Sampling, Degarelix Investigators will assess the change in inhibin B levels following repeated bolus dosing of recombinant FSH (rFHS) following Degarelix (GnRH antagonist) blockade over a 2-day period. This arm was terminated due to Adverse Events and the study was continued with the Cetrorelix product.
BMI = 18.5 to 24.9 BMI | 6 |
| Experimental: Frequent Blood Sampling, Cetrorelix: Normal Weight Investigators will assess the change in inhibin B levels following repeated bolus dosing of recombinant FSH (rFHS) following Cetrorelix blockade over a 2-day period.
Normal weight participants = 18.5 to 24.9 BMI | 27 |
| Experimental: Frequent Blood Sampling, Cetrorelix: Obese Investigators will assess the change in inhibin B levels following repeated bolus dosing of recombinant FSH (rFHS) following Cetrorelix blockade over a 2-day period.
Obese participants = BMI of \>30 | 27 |
| Total | 60 |
Baseline characteristics
| Characteristic | Experimental: Frequent Blood Sampling, Degarelix | Total | Experimental: Frequent Blood Sampling, Cetrorelix: Obese | Experimental: Frequent Blood Sampling, Cetrorelix: Normal Weight |
|---|---|---|---|---|
| Age, Continuous | 29.5 years STANDARD_DEVIATION 5.9 | 29.6 years STANDARD_DEVIATION 5 | 31.9 years STANDARD_DEVIATION 4.1 | 27.2 years STANDARD_DEVIATION 4.7 |
| BMI | 22.5 kg/m^2 STANDARD_DEVIATION 2.5 | 30.1 kg/m^2 STANDARD_DEVIATION 8.9 | 37.7 kg/m^2 STANDARD_DEVIATION 6.2 | 22.4 kg/m^2 STANDARD_DEVIATION 1.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 6 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 54 Participants | 24 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 7 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 49 Participants | 20 Participants | 24 Participants |
| Region of Enrollment United States | 6 participants | 60 participants | 27 participants | 27 participants |
| Sex: Female, Male Female | 6 Participants | 60 Participants | 27 Participants | 27 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Weight | 59.8 kg STANDARD_DEVIATION 4.2 | 81.6 kg STANDARD_DEVIATION 24.9 | 102 kg STANDARD_DEVIATION 19.3 | 61.1 kg STANDARD_DEVIATION 5.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 5 / 6 | 0 / 27 | 0 / 27 |
| serious Total, serious adverse events | 0 / 6 | 0 / 27 | 0 / 27 |
Outcome results
Primary
Difference Between Peak Inhibin B
This is defined as the maximum hormone value during Day 1 of the study subtracted from the maximum hormone value during Day 2.
Time frame: Every 10 minutes over 2 10-hour frequent blood sampling sessions.
Population: The Degarelix arm is excluded because no data was collected from those participants. The Degarelix arm was terminated due to adverse events and was replaced with the Cetrorelix arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Frequent Blood Sampling, Cetrorelix: Normal Weight | Difference Between Peak Inhibin B | 100.8 picograms/mL | Standard Deviation 73.7 |
| Experimental: Frequent Blood Sampling, Cetrorelix: Obese | Difference Between Peak Inhibin B | 38.8 picograms/mL | Standard Deviation 37.9 |
Secondary
Peak E2 Per Subject
E2 will be measured every 10 minutes on Day 1 and Day 2 of the study. The highest E2 value will be designated as the peak E2 value.
Time frame: Every 10 minutes over 10 hours of Day 1 and Day 2 of the study.
Population: The Degarelix arm is excluded because no data was collected from those participants. The Degarelix arm was terminated due to adverse events and was replaced with the Cetrorelix arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Frequent Blood Sampling, Cetrorelix: Normal Weight | Peak E2 Per Subject | Day 1 | 65.1 pg/L | Standard Deviation 58 |
| Experimental: Frequent Blood Sampling, Cetrorelix: Normal Weight | Peak E2 Per Subject | Day 2 | 137.7 pg/L | Standard Deviation 61.8 |
| Experimental: Frequent Blood Sampling, Cetrorelix: Obese | Peak E2 Per Subject | Day 1 | 72.5 pg/L | Standard Deviation 37.7 |
| Experimental: Frequent Blood Sampling, Cetrorelix: Obese | Peak E2 Per Subject | Day 2 | 99.1 pg/L | Standard Deviation 41.6 |
Secondary
Peak Inhibin B Per Subject
Peak inhibin B will be measured every 10 minutes during day 1 and day 2 of the study. The highest inhibin B value will be defined as the peak.
Time frame: Every 10 minutes over 10 hours on Day 1 and Day 2 of the study.
Population: The Degarelix arm is excluded because no data was collected from those participants. The Degarelix arm was terminated due to adverse events and was replaced with the Cetrorelix arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Frequent Blood Sampling, Cetrorelix: Normal Weight | Peak Inhibin B Per Subject | Day 1 maximum | 103.5 picograms/mL | Standard Deviation 43.8 |
| Experimental: Frequent Blood Sampling, Cetrorelix: Normal Weight | Peak Inhibin B Per Subject | Day 2 maximum | 226.5 picograms/mL | Standard Deviation 105.3 |
| Experimental: Frequent Blood Sampling, Cetrorelix: Obese | Peak Inhibin B Per Subject | Day 1 maximum | 87.5 picograms/mL | Standard Deviation 45.3 |
| Experimental: Frequent Blood Sampling, Cetrorelix: Obese | Peak Inhibin B Per Subject | Day 2 maximum | 126.3 picograms/mL | Standard Deviation 52.5 |