Weight Loss Comparison on Fertility and Pregnancy Outcomes

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Weight Loss Comparison on Fertility and Pregnancy Outcomes

SUMMARY: CAN WEIGHT LOSS INCREASE FERTILITY

In this study, obese women who lost 10-15% of weight, instead of only 3% prior to pregnancy, had significantly higher rates of pregnancy (70 vs. 60 %), improved live birth rates (49 vs. 42 %), less adverse pregnancy outcomes and healthier newborn weights.

doi.org/10.1002/oby.23200

Background

High BMI (Body Mass Index) among women has long been associated with poor pregnancy outcomes. It has also been reported that maternal obesity potentially impacts the health of the offspring both in the short and long-term. 

Experts suggest obese women consider losing weight by following a proper diet and exercising. However, studies show that these changes lead to only a 3% decrease in body weight. This small change in weight improves fertility but it does not enhance pregnancy outcomes. 

More recent studies revealed that obese women need to lose at least 10-15% of weight for their pregnancy outcomes to improve significantly. Bariatric surgery is one method to achieve this weight-loss goal, however, it also increases the risk of SGA (small for gestational age) and early offspring death.

Another strategy is for women to go on a very low-energy diet (VLED) over 2-3 months, however the potential effect of VLED on pregnancy outcomes is still not well-researched.

Aim

To analyse the effectiveness of a nonsurgical preconception treatment (VLED) on weight loss and pregnancy outcomes in women suffering from obesity.

Methodology

In this two-arm, parallel-group, randomized control study, women with a BMI of 30-55 and planning pregnancy in 6 to 12 months were recruited using social media. Women who required ART (Assisted Reproductive Technology) were included, if the treatment occurred after the study, along with any women diagnosed with polycystic ovarian syndrome and those taking a stable dose of metformin.

Exclusion criteria included women: 

  • who were pregnant 
  • with irreversible infertility 
  • with diabetes 
  • who were taking medications that could affect weight 
  • with other significant illnesses 

Eligible women (n=164) were randomly assigned into 2 study groups, standard dietary intervention (SDI) and very low-energy diet (VLED).

The study was carried out in 3 phases: 

  • Phase 1: Weight-loss phase (Weeks 0-12)
  • Phase 2: Weight maintenance phase (Weeks 13-16)
  • Phase 3 
    • Phase 3A: Prepregnancy phase (Weeks 17-60)
    • Phase 3B: Pregnancy

Only the VLED formulation by Nestle S.A. was provided to these participants.

Weight, bioimpedance, blood ketones and urine pregnancy tests were carried out fortnightly during the first 12 weeks. The participants also wore a pedometer, for a minimum of 7 consecutive days, and were asked to aim for at least 10,000 steps daily. 

At the end of Phase 1, the participants were then given individual counselling on weight maintenance by a dietitian.  

This prepared participants for Phase 2 which was stabilize their weight and prepare their bodies for conception. At the end of Week 16, weight, bioimpedance, blood ketones and urine pregnancy tests were carried out again.

During Phase 3A (Weeks 17-60), study visits was carried out every 12 weeks where urinary pregnancy tests were performed and further dietary advice provided. The participants were also encouraged to maintain an active lifestyle (over 10,000 steps per day).

All participants were instructed to use approved forms of contraception until the end of Phase 2 (Weight maintenance phase) and given oral supplements, folate (5mg) and a multivitamin with 150μg of iodine, until at least week 12 of pregnancy. 

Any positive home pregnancy test was reported to the study site and pregnant participants followed throughout phase 3B. Medical and obstetric data was collected during this phase with maternal and neonatal-outcomes taken from the birth discharge summary. 

All study visits were done between 8:00 AM and 10:00 AM in the fasting state with body measurements taken in light clothing and barefoot. Weight was checked using calibrated digital scales while bioelectrical impedance was utilised for body composition. Fasting glucose assays were carried out according established protocols. 

Maternal fasting plasma glucose at 26 to 28 weeks of gestation was considered the primary study outcome, with other harmful obesity-related pregnancy outcomes also explored.

Pregnancies that occurred during the intervention (0-12 weeks), and multifetal pregnancies, were not considered for analysis.

Results

Initial analysis prior to study commencement revealed no statistically significant differences in the baseline measurements of the 2 groups (SDI [n=79] and VLED [n= 85]).

Among the 164 initial participants, 35 did not complete the initial intervention (Phase 1) and 5 achieved pregnancy during the intervention. These 40 women were subsequently excluded from the completers-only analysis.

By week 12, there was a significant difference in weight loss between the 2 groups, with a 3.2kg in loss in the SDI group and 13.0kg loss in the VLED group.

This difference in weight was maintained during Phase 2 and Phase 3, with the small difference in weight gain between the 2 groups not statistically significant.

Weight gainSDIVLED
Phase 23.0 kg3.6 kg
Phase 310.9 kg10.3 kg

Initial analysis of outcomes among study completers (n=124), revealed 82 women achieved pregnancy (SDI: n= 32/53, VLED: n= 50/71) resulting in 57 live births (SDI: n = 22/53, VLED: n = 35/71).

The median time to pregnancy was 140.5 days in the SDI group but only 51.0 days in the VLED group.

SDIVLEDP-value
Completers53710.26
Total pregnancy in completers32 (60%)50 (70%)0.03
Pregnancy resulting in miscarriage10 (31%)13 (26%)0.66
Pregnancy resulting in live birth22 (42%)35 (49%)0.10
Multiple pregnancy (excluded)020.50
Not pregnant21210.85


The 75-g OGTT (oral glucose tolerance test) between 26 and 28 weeks gestation show no significant difference in fasting glucose and 1-hour post glucose load between the 2 groups. However, participants in the SDI group had a significantly higher 2-hours post glucose load than the women from the VLED group, indicating poorer glucose tolerance.

SDIVLEDP-value
Fasting glucose (mmol/L) 4.84.60.42
1-hr glucose (mmol/L) 7.97.40.42
2-hr glucose (mmol/L) 6.75.90.04

When the array of obesity-related pregnancy outcomes was analysed, the SDI group had significantly higher adverse pregnancy outcomes compared to the VLED group. (SDI: 38 events in 22 participants; VLED: 24 events in 35 participants). 

No significant difference between the groups was found in terms of total caesarean-section rate, primary caesarean-section rate, neonatal SCN/ICU length of stay and maternal length of stay among study completers who achieved pregnancy. 

However statistical analysis did show that offsprings in the SDI group had significantly higher (median) birth weights compared to the VLED group. 

Limitations

  1. Small study size.
  2. Possible presence of live-birth bias due to spontaneous abortions.

Funding

The study was funded by the Norman Beischer Medical Research Foundation and the National Health and Medical Research Council. 

Glossary

Assay
A laboratory test.

Bioimpedance
The electrical properties of a biological medium.

ICU
Intensive Care Unit

Median
The middle number of a sorted data set.

Multifetal
Multiple.

n
Sample size.

Neonate
Newborn child.

P-value
The probability that a result occurred by random chance.

Pedometer
Step counter.

SCN
Special Care Nursery

Similar studies

Lowe W L, et al. (2019). Maternal glucose levels during pregnancy and childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study. https://doi.org/10.1007/s00125-018-4809-6

Schummers L, et al. (2015). Risk of adverse pregnancy outcomes by prepregnancy body mass index: a population-based study to inform prepregnancy weight loss counseling. https://doi.org/10.1097/aog.0000000000000591

Callaway L K, et al. (2006). The prevalence and impact of overweight and obesity in an Australian obstetric population. https://doi.org/10.5694/j.1326-5377.2006.tb00115.x

Boney C M, et al. (2005). Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. https://doi.org/10.1542/peds.2004-1808


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