GDM, Glucose Intolerance, Insulin Resistance, Obesity, PCOS
Conditions
Keywords
IVF, Glucose Homeostasis, Metabolic Parameters
Brief summary
A quantitative prospective cohort study will be conducted, where blood samples will be collected at different timings during the IVF protocol, to assess the impact of fertility medications on metabolic parameters of patients undergoing IVF treatment.
Detailed description
Numerous factors predispose women to develop pregnancy-related complications, these include gestational diabetes (GDM), pre-pregnancy obesity, advanced maternal age (\> 35 years) and gestational age, abnormal weight gain during pregnancy, family history of diabetes, PCOS and low parity. Evidenced-based studies reported that women with PCOS have a significantly higher risk of developing GDM compared with women without PCOS, independently of the obesity factor; this risk is higher when both factors coexist. Given the known effect of reproductive hormones on weight-gain, controversies still exist on whether ART predispose women to more adverse obstetric outcomes compared to normal pregnancy. ART describes different procedures to help women become pregnant, with In Vitro Fertilization (IVF) being the most commonly performed. It has been demonstrated that IVF is associated with glucose intolerance in mice and it will be interesting to determine whether this physiologic phenomenon is also altered by IVF medication (such as estrogen and progesterone) in humans. While some studies reported that singleton pregnancies conceived by ART (IVF or ovulation induction) were strongly associated with GDM compared to spontaneous conceptions, other studies did not find significant differences in the risk of GDM. Increased GDM risk presented with IVF can be associated with prenatal obesity or secondary to maternal PCOS condition. The former studies did not specify the body mass index (BMI) and the medical history of participants undergoing IVF, such as the presence of PCOS. Due to limited available data, we still cannot distinguish whether these adverse pregnancy outcomes are due to the pre-existing conditions such as PCOS, or are secondary to the IVF therapy itself.
Interventions
DIAGNOSTIC_TESTHbA1C
After overnight fasting, 10 ml of blood will be collected at four different timings during the IVF protocol: 1. At baseline (second day of the menstrual period) 2. Triggering phase (post-egg retrieval procedure) 3. Embryo transfer phase (post-transfer procedure) 4. Week 4 (positive bHCG) 4\. Week 8 of pregnancy
Sponsors
Fakih IVF Fertility Center
University of Sharjah
University of Warwick
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 39 Years
Healthy volunteers
Yes
Inclusion criteria
Any patient presenting to us for fresh IVF with the following: Inclusion Criteria: * Presenting with or without PCOS * Presenting with structural or mechanical infertility, such as fallopian tube obstruction, endometriosis, fibroids * Presenting with male factor * Presenting with or without insulin resistance * Combination of more than one of the listed above criteria
Exclusion criteria
* Pre-diabetes or diabetes patients (confirmed by impaired or abnormal OGTT) * Age above 39 years of age * Taking glucose-lowering meds, such as metformin or janumet. * Taking corticosteroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Short-term Effect of Fertility Medications on Glucose Homeostasis and Insulin Resistance in Patients Undergoing IVF Treatment | 12 weeks of pregnancy | Participants who experience an abnormal increase in fasting glucose (\>110) and A1C (\>5.7) will be identified post-treatment. Also, for those previously known to be insulin-resistant, HOMA ratio will help identifying whether the treatment worsens or has no effect on their insulin resistance state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Fertility Medications on Lipids Profile | 12 weeks of pregnancy | Lipid profile will be measured before and after treatment; participants experiencing hypercholesterolemia post-treatment will be consulted by a dietitian to help them better manage the condition during their pregnancy (total chol, LDL and triglycerides) |
| Effect of Fertility Medications on Thyroid Function | 12 weeks of pregnancy | TSH level will be measured pre- and post-IVF. Early diagnosis of thyroid dysfunction will be closely monitored with frequent repetitions of blood test, especially during the first trimester. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Long-term Effect of Fertility Medications in Relation to Maternal and Fetal Outcomes | 9 months of pregnancy | Early management and/control of metabolic-related adverse outcomes in relation to IVF treatment will prevent GDM by for instance glucophage administration or regular blood test of TSH for participants reported to be at higher risk of thyroid dysfunction. |
Countries
United Arab Emirates
Participant flow
Pre-assignment details
702screened --\>673eligible to start IVF--\>359 had embryo transfer --\>191clinically confirmed pregnant+158 negative β-HCG+10 biochem pregnancy--\> 64drop-outs+10 miscarriage--\> Completed study and included in data: 158 pregnant+117 non-pregnant women
Participants by arm
| Arm | Count |
|---|---|
| Non-Pregnant Negative BHCG at 4 weeks | 117 |
| Pregnant Positive BHCG at 4 weeks | 158 |
| Total | 275 |
Baseline characteristics
| Characteristic | Pregnant | Total | Non-Pregnant |
|---|---|---|---|
| Age, Continuous | 32 years | 32.3 years | 32.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 25 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 17 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 134 Participants | 233 Participants | 99 Participants |
| Sex: Female, Male Female | 158 Participants | 275 Participants | 117 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 117 | 0 / 158 |
| other Total, other adverse events | 0 / 117 | 0 / 158 |
| serious Total, serious adverse events | 0 / 117 | 0 / 158 |
Outcome results
Primary
Short-term Effect of Fertility Medications on Glucose Homeostasis and Insulin Resistance in Patients Undergoing IVF Treatment
Participants who experience an abnormal increase in fasting glucose (\>110) and A1C (\>5.7) will be identified post-treatment. Also, for those previously known to be insulin-resistant, HOMA ratio will help identifying whether the treatment worsens or has no effect on their insulin resistance state.
Time frame: 12 weeks of pregnancy
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Non-Pregnant | Short-term Effect of Fertility Medications on Glucose Homeostasis and Insulin Resistance in Patients Undergoing IVF Treatment | Glucose, fasting | 87.62 mg/dL |
| Non-Pregnant | Short-term Effect of Fertility Medications on Glucose Homeostasis and Insulin Resistance in Patients Undergoing IVF Treatment | Insulin, fasting | 9.37 mg/dL |
| Pregnant | Short-term Effect of Fertility Medications on Glucose Homeostasis and Insulin Resistance in Patients Undergoing IVF Treatment | Glucose, fasting | 82.19 mg/dL |
| Pregnant | Short-term Effect of Fertility Medications on Glucose Homeostasis and Insulin Resistance in Patients Undergoing IVF Treatment | Insulin, fasting | 9.45 mg/dL |
Secondary
Effect of Fertility Medications on Lipids Profile
Lipid profile will be measured before and after treatment; participants experiencing hypercholesterolemia post-treatment will be consulted by a dietitian to help them better manage the condition during their pregnancy (total chol, LDL and triglycerides)
Time frame: 12 weeks of pregnancy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-Pregnant | Effect of Fertility Medications on Lipids Profile | 199.5 mg/dL |
| Pregnant | Effect of Fertility Medications on Lipids Profile | 174.9 mg/dL |
Secondary
Effect of Fertility Medications on Thyroid Function
TSH level will be measured pre- and post-IVF. Early diagnosis of thyroid dysfunction will be closely monitored with frequent repetitions of blood test, especially during the first trimester.
Time frame: 12 weeks of pregnancy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-Pregnant | Effect of Fertility Medications on Thyroid Function | 1.36 μIU/mL |
| Pregnant | Effect of Fertility Medications on Thyroid Function | 1.80 μIU/mL |
Other Pre-specified
Long-term Effect of Fertility Medications in Relation to Maternal and Fetal Outcomes
Early management and/control of metabolic-related adverse outcomes in relation to IVF treatment will prevent GDM by for instance glucophage administration or regular blood test of TSH for participants reported to be at higher risk of thyroid dysfunction.
Time frame: 9 months of pregnancy