The Effects of an Intensive Lifestyle Intervention on Reproductive Outcomes
| Status: | Completed |
|---|---|
| Conditions: | Obesity Weight Loss, Women's Studies |
| Therapuetic Areas: | Endocrinology, Reproductive |
| Healthy: | No |
| Age Range: | 18 - 35 |
| Updated: | 4/21/2016 |
| Start Date: | July 2013 |
| End Date: | July 2015 |
The Effects of an Intensive Lifestyle Intervention on Reproductive Outcomes in Obese, Subfertile Women
This is a study to determine whether a low calorie diet using meal replacement shakes
compared to current counseling about diet, followed by 3 cycles of clomiphene citrate (if
needed) will result in: 1) improvements in ability to ovulate and achieve pregnancy either
spontaneously or during 3 clomiphene citrate cycles 2) greater weight loss with reductions
in waist and hip circumferences and improvements in hormones that are involved in allowing
pregnancy to occur and hormones that are involved in metabolism, such as insulin and glucose
(sugar) 3) improvements in other health conditions such as blood pressure, and emotional and
physical well-being.
Women eligible to participate will be between the ages of 18-35 with a BMI (ratio of weight
in kg divided by height in m2) of ≥ 35≤45 kg/m2 who are seeking help for anovulatory
infertility including women with a diagnosis of polycystic ovarian syndrome (PCOS).
compared to current counseling about diet, followed by 3 cycles of clomiphene citrate (if
needed) will result in: 1) improvements in ability to ovulate and achieve pregnancy either
spontaneously or during 3 clomiphene citrate cycles 2) greater weight loss with reductions
in waist and hip circumferences and improvements in hormones that are involved in allowing
pregnancy to occur and hormones that are involved in metabolism, such as insulin and glucose
(sugar) 3) improvements in other health conditions such as blood pressure, and emotional and
physical well-being.
Women eligible to participate will be between the ages of 18-35 with a BMI (ratio of weight
in kg divided by height in m2) of ≥ 35≤45 kg/m2 who are seeking help for anovulatory
infertility including women with a diagnosis of polycystic ovarian syndrome (PCOS).
More than 33% of U.S. adults over the age of 20 are obese (BMI ≥30 kg/m2), and 6% are
severely obese (BMI ≥40 kg/m2). As the prevalence and severity of obesity has increased, so
has the number of women who have obesity-related abnormalities in reproductive function,
including anovulation and infertility. Specifically, obesity contributes to ovulatory
problems and compromises ovarian response to ovulation induction agents such as clomiphene.
Women seeking assistance from specialists for reproductive concerns are both anxious to
achieve pregnancy and highly motivated. We propose to assess the relative efficacy of very
low energy diet (VLED) using liquid meal replacement vs. standard of care dietary counseling
and education (DCE) on the metabolic effects of weight reduction in the obese, subfertile
population and assess ovulation and time to conception in these women. We hypothesize that
use of a very low energy diet with resultant rapid and profound weight loss and marked
improvement in metabolic state, will increase the rate of spontaneous cycling, improve
unassisted and clomiphene-assisted ovulation and significantly improve conception and
pregnancy rates. Because of the direct relationship between obesity and anovulation, we will
test whether evaluation of both habitual dietary intake and plasma metabolomic profiles can
be used to identify specific dietary components and metabolites that predict successful or
unsuccessful induction of ovulation and pregnancy in response to weight loss with or without
clomiphene citrate.
32 reproductive age women with a BMI ≥35≤45 kg/m2 will be randomized to 12 weeks of VLED or
DCE and ovulation rates and time to conception between groups will be assessed over a 6
month period. We will also evaluate between group differences in rate of weight loss,
absolute weight lost, BMI, waist and hip circumferences as well as reproductive and
metabolic hormone levels. Luteinizing hormone (LH), follicle stimulating hormone (FSH),
androgens, leptin, glucose and insulin (HOMA), and β-cell function (Matsuda Index).
We will assess if clinical, hormonal, dietary or metabolomic profiles, can predict response
to weight loss or clomiphene citrate in improving ovulation. Women will be assessed for
clinical and molecular phenotypes, including plasma metabolomic profiles. Metabolomic
profiles will be adjusted for chronic dietary intake. An initial assessment of the levels of
dietary components, metabolites or metabolic pathways that predict response will be
investigated.
We will determine program acceptability and differences in the change in co-morbid health
conditions, quality-of-life, and psychological well-being in standard of care and VLED-based
weight loss participants. Important physiological benefits arise from weight loss and the
magnitude of these changes will be assessed in the group of patients seeking reproductive
assistance.
This pilot study will provide the first information on the relative success of aggressive,
short-term weight loss in the treatment of infertility as defined by improvement in
ovulation and conception and provide data for larger, definitive trials of this approach.
The study will allow assessment of the feasibility and acceptability of translating VLED
treatment-based clinical care and research developed by the University of Michigan
Investigational Weight Management Clinic to a specialized population seeking reproductive
assistance. Finally, this study will provide important preliminary data for a larger trial
to assess the health effects on the mother and the offspring as a result of aggressive
intervention to alter the pre-pregnancy metabolic environment in reproductive age women.
severely obese (BMI ≥40 kg/m2). As the prevalence and severity of obesity has increased, so
has the number of women who have obesity-related abnormalities in reproductive function,
including anovulation and infertility. Specifically, obesity contributes to ovulatory
problems and compromises ovarian response to ovulation induction agents such as clomiphene.
Women seeking assistance from specialists for reproductive concerns are both anxious to
achieve pregnancy and highly motivated. We propose to assess the relative efficacy of very
low energy diet (VLED) using liquid meal replacement vs. standard of care dietary counseling
and education (DCE) on the metabolic effects of weight reduction in the obese, subfertile
population and assess ovulation and time to conception in these women. We hypothesize that
use of a very low energy diet with resultant rapid and profound weight loss and marked
improvement in metabolic state, will increase the rate of spontaneous cycling, improve
unassisted and clomiphene-assisted ovulation and significantly improve conception and
pregnancy rates. Because of the direct relationship between obesity and anovulation, we will
test whether evaluation of both habitual dietary intake and plasma metabolomic profiles can
be used to identify specific dietary components and metabolites that predict successful or
unsuccessful induction of ovulation and pregnancy in response to weight loss with or without
clomiphene citrate.
32 reproductive age women with a BMI ≥35≤45 kg/m2 will be randomized to 12 weeks of VLED or
DCE and ovulation rates and time to conception between groups will be assessed over a 6
month period. We will also evaluate between group differences in rate of weight loss,
absolute weight lost, BMI, waist and hip circumferences as well as reproductive and
metabolic hormone levels. Luteinizing hormone (LH), follicle stimulating hormone (FSH),
androgens, leptin, glucose and insulin (HOMA), and β-cell function (Matsuda Index).
We will assess if clinical, hormonal, dietary or metabolomic profiles, can predict response
to weight loss or clomiphene citrate in improving ovulation. Women will be assessed for
clinical and molecular phenotypes, including plasma metabolomic profiles. Metabolomic
profiles will be adjusted for chronic dietary intake. An initial assessment of the levels of
dietary components, metabolites or metabolic pathways that predict response will be
investigated.
We will determine program acceptability and differences in the change in co-morbid health
conditions, quality-of-life, and psychological well-being in standard of care and VLED-based
weight loss participants. Important physiological benefits arise from weight loss and the
magnitude of these changes will be assessed in the group of patients seeking reproductive
assistance.
This pilot study will provide the first information on the relative success of aggressive,
short-term weight loss in the treatment of infertility as defined by improvement in
ovulation and conception and provide data for larger, definitive trials of this approach.
The study will allow assessment of the feasibility and acceptability of translating VLED
treatment-based clinical care and research developed by the University of Michigan
Investigational Weight Management Clinic to a specialized population seeking reproductive
assistance. Finally, this study will provide important preliminary data for a larger trial
to assess the health effects on the mother and the offspring as a result of aggressive
intervention to alter the pre-pregnancy metabolic environment in reproductive age women.
Inclusion Criteria:
- Women
- 18 to 35 years old
- Obese(BMI of ≥35≤45 kg/m2)
- Infertility (12 months of unprotected intercourse without conception)
- Ovulatory dysfunction (amenorrhea, irregular cycles, or progesterone level less than
10 ng/mL in the luteal phase)
- Partner with semen analysis demonstrating at least 20 million sperm/mL, 50% motility,
and normal morphology by Kruger criteria of 8%
- Evidence of normal uterine anatomy and at least on patent tube documented by
hysterosalpingogram or saline infusion sonogram.
- Women with polycystic ovary syndrome
Exclusion Criteria:
- Significant heart disease (coronary artery disease, Class II-VI Heart Failure,
arrythmia)
- Chronic Kidney Disease, Stage IV or greater
- Significant gastrointestinal tract diseases (e.g. IBD)
- Autoimmune disorders (e.g. systemic lupus erythematosus)
- Neurological (e.g. Multiple Sclerosis)
- Psychiatric disorders (Bipolar, Major Depression)
- History of or current eating disorders or substance abuse
- Endocrine disorders (Type 1 diabetes, adrenal, pituitary or uncontrolled thyroid
disease)
- HIV/AIDS
- Significant anemia
- History of or current clotting disorder
- Cancer other than minor skin cancers
- Other conditions that would complicated pregnancy.
- Women will be excluded if they are taking anti-obesity drugs, or appetite
suppressants within the last 2 months, or have had previous bariatric surgery.
- Women will be excluded if they have used hormonal medications within the last 2
months, previous use of ovulation induction medications, have endometriosis by
American Fertility Society (AFS) class III or IV, have an FSH > 10 IU/mL or couples
using donor sperm or are already pregnant.
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