IVF: In Vitro Fertilization Impact on Metabolic Parameters

• Sponsor: University of Warwick (Other)
• Overall Status: Completed
• CT.gov ID: NCT03426228
• Collaborator: Fakih IVF Fertility Center (Other), University of Sharjah (Other)
• Enrollment: 344
• Location: 1
• Actual Duration (Months): 22.6
• Patients Per Site Per Month: 15.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
GDM; Insulin Resistance; Glucose Intolerance; PCOS; Obesity	Diagnostic Test: HbA1C

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.

Study Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 344 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Effects of Fertility Drugs on Glucose Homeostasis and Other Metabolic Parameters on Patients Undergoing In Vitro Fertilization (IVF)
• Actual Study Start Date: Feb 15, 2018
• Actual Primary Completion Date: Aug 1, 2019
• Actual Study Completion Date: Jan 5, 2020

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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)

2. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 39 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fakih IVF	Dubai		United Arab Emirates	72960

Sponsors and Collaborators

• University of Warwick
• Fakih IVF Fertility Center
• University of Sharjah

Investigators

• Principal Investigator: Ayla Coussa, Dietitian, Fakih IVF Dubai

Study Documents (Full-Text)

• Study Protocol - Dec 15, 2019
• Statistical Analysis Plan - Dec 15, 2019
• Informed Consent Form - Jan 5, 2018

More Information

Publications

• Coussa A, Hasan HA, Barber TM. Effects of in vitro fertilization (IVF) therapies on metabolic, endocrine and inflammatory status in IVF-conceived pregnancy. Clin Endocrinol (Oxf). 2020 Dec;93(6):705-712. doi: 10.1111/cen.14270. Epub 2020 Jul 9.

• Responsible Party: Ayla Coussa, MSc., University of Warwick
• ClinicalTrials.gov Identifier: NCT03426228
• Other Study ID Numbers: DSREC-11/2017_09
• First Posted: Feb 8, 2018
• Last Update Posted: Jul 14, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ayla Coussa, MSc., University of Warwick: IVF, Glucose Homeostasis, Metabolic Parameters
• Additional relevant MeSH terms: Insulin Resistance; Glucose Intolerance; Progesterone; Estrogens

Study Results

Participant Flow

Pre-assignment Detail	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

Arm/Group Title	Non-Pregnant	Pregnant
Arm/Group Description	Negative BHCG at 4 weeks	Positive BHCG at 4 weeks
Period Title: Overall Study
STARTED	158	191
COMPLETED	117	158
NOT COMPLETED	41	33

Baseline Characteristics

Arm/Group Title	Non-Pregnant	Pregnant	Total
Arm/Group Description	Negative BHCG at 4 weeks	Positive BHCG at 4 weeks	Total of all reporting groups
Overall Participants	117	158	275
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	32.5	32	32.3
Sex: Female, Male (Count of Participants)
Female	117 100%	158 100%	275 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	9 7.7%	16 10.1%	25 9.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	9 7.7%	8 5.1%	17 6.2%
White	99 84.6%	134 84.8%	233 84.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Short-term Effect of Fertility Medications on Glucose Homeostasis and Insulin Resistance in Patients Undergoing IVF Treatment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-Pregnant	Pregnant
Arm/Group Description	Negative BHCG at 4 weeks	Positive BHCG at 4 weeks
Measure Participants	117	158
Glucose, fasting	87.62	82.19
Insulin, fasting	9.37	9.45

2. Secondary Outcome

Title	Effect of Fertility Medications on Lipids Profile
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pregnant	Non-pregnant
Arm/Group Description	Positive BHCG at 4 weeks	Negative BHCG at 4 weeks
Measure Participants	158	117
Median (Inter-Quartile Range) [mg/dL]	199.5	174.9

3. Secondary Outcome

Title	Effect of Fertility Medications on Thyroid Function
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pregnant	Non-pregnant
Arm/Group Description	Positive BHCG at 4 weeks	Negative BHCG at 4 weeks
Measure Participants	158	117
Median (Inter-Quartile Range) [μIU/mL]	1.36	1.80

4. Other Pre-specified Outcome

Title	Long-term Effect of Fertility Medications in Relation to Maternal and Fetal Outcomes
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	9 months
Adverse Event Reporting Description	Study is observational and non-experimental. No invasive procedures were used.
Arm/Group Title	Non-Pregnant		Pregnant
Arm/Group Description	Negative BHCG at 4 weeks		Positive BHCG at 4 weeks
All Cause Mortality
	Non-Pregnant		Pregnant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/117 (0%)		0/158 (0%)
Serious Adverse Events
	Non-Pregnant		Pregnant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/117 (0%)		0/158 (0%)
Other (Not Including Serious) Adverse Events
	Non-Pregnant		Pregnant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/117 (0%)		0/158 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.