Weight Loss Before IVF Shows Some Benefits

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Weight Loss Before IVF Shows Some Benefits

SUMMARY: DOES WEIGHT LOSS INCREASE IVF SUCCESS

In this study, women who lost 4kg of weight before IVF had higher live birth success rates (26% vs. 18%), due to lower rates of miscarriage (7% vs. 35%), along with lower rates of large for gestational age newborn (15% vs. 31%).

doi.org/10.1093/hropen/hoab032

Background

Over the last few years, several studies have reported a link between obesity and lower birth rates following in vitro fertilisation (IVF).

While the underlying mechanisms are still under investigation, one study observed that the oocytes of women suffering from obesity, were smaller and reached the morula stage faster, than oocytes from normal-weight participants.

They also noted that internal triglyceride levels and glucose intake of these oocytes was abnormal at the blastocyst stage, which explains somewhat the irregular metabolism of these embryos.

Other studies suggest that differences in follicular fluid composition between obese women and non-obese women could be the cause of poor oocyte quality leading to impaired development.

In fact maternal obesity has been linked to several negative neonatal outcomes including gestational diabetes, pre-eclampsia, large for gestational age (LGA) babies and congenital anomalies.

It is therefore quite normal for health experts to recommend women improve their health before infertility treatment. However, evidence on the effectiveness of lifestyle changes and weight loss prior to IVF is quite scarce.

Methodology

To determine whether lifestyle intervention improves embryo quality, expressed as embryo utilization rate (EUR) and cumulative live birth rate (CLBR) following the first fresh and subsequent frozen-thawed embryo transfers.

Methodology

A nested cohort study of the randomised controlled trial named LIFEstyle was carried out. Infertile women with BMI ≥29 kg/m2 received explorative fertility investigation, prior to study randomization, to establish the appropriate infertility treatment.

After randomization, participants in the intervention group began the lifestyle intervention to reduce body weight by at least 5% (or BMI <29 kg/m2), while those in the control group continued treatment as usual.

Local hospital guidelines were followed when choosing and performing IVF or ICSI under controlled ovarian stimulation (COS) or modified nature cycle (MNC).

Embryo development was monitored daily after fertilisation with embryo transfer subsequently carried out on Day 2, 3 or 4. A maximum of 2 embryos was transferred and all supplementary embryos cryopreserved, if they passed the minimum quality threshold, set by the respective IVF centre.

Following a positive pregnancy test, a vaginal sonography was performed approximately 4 weeks after embryo transfer. On the other hand, in cases of a negative pregnancy test, frozen embryos were then thawed and transferred until pregnancy was achieved or the last embryo transferred.

A number of oocyte/embryo parameters were recorded including:

  • Number of oocytes retrieved 
  • Number of oocytes inseminated/injected 
  • Number of oocytes fertilized 
  • Number of normal fertilized embryos 
  • Day of embryo transfer
  • Number of transferred embryos 
  • Number of cryopreserved embryos  
  • Embryo utilization rate (EUR) 

EUR was defined as the proportion of inseminated/injected oocytes per cycle that was transferred or cryopreserved as an embryo. 

Neonatal outcomes included birthweight, gestational age, gender, small for gestational age (SGA) or large for gestational age (LGA). 

In cases where the initial cycle was cancelled due to poor response or expected ovarian hyperstimulation syndrome, the following cycle with successful oocyte retrieval was used for analysis.

Results

Of the 158 participants, only 51 women from the intervention group and 72 in the control group were considered for analysis. The other 35 women were either lost to follow-up, had cancelled cycles or ended up conceiving naturally.

Baseline analysis showed no significant age (32.5 vs. 32.2 years, P=0.74) or BMI (35.4 vs. 34.9 kg/m2, P=0.33) difference between the intervention and control groups.

However, there was significant differences between the 2 groups according to infertility diagnosis (unexplained and male factor) and smoking habits.

 LIFEstyle intervention
(n=51) 
Control
(n=72) 
P-Value 
Type of infertility
Anovulation4 (7.8%)9 (12.5%)0.41
Unexplained5 (9.8%)21 (29.2%)0.01
Male factor38 (74.5%)39 (54.2%)0.02
Tubal factor8 (15.7%)9 (12.5%)0.61
Smoking18 (35.3%)13 (18.1%)0.03
Baseline characteristics of participants. (P≤0.05, statistically significant)

At the end of the 6-month lifestyle intervention, body weight measurements confirmed a statistically significant difference, in the mean weight change between the 2 groups, favouring the intervention group.

Data obtained in regards to stimulation methods (COS or MNC), controlled ovarian stimulation regimes and FSH dosage, confirmed no statistically significant differences between the 2 groups.

Mean number of oocytes retrieved, inseminated or injected, and number of normal fertilized embryos were also similar (P>0.05).

Interestingly, EUR was 33.33% in the per cycle analysis for both groups, however per oocyte/embryo analysis did show a non-statistically significant improvement in EUR following LIFEstyle intervention.

LIFEstyle intervention
(n=51)
Control
(n=72)
Weight change at 6 months after intervention (kg)-3.95-0.80
Number of Oocytes retrieved4.006.00
Number of oocytes inseminated/injected4.006.00
Number of normal fertilized embryos2.003.00
Number of embryo cryopreserved2.002.00
EUR – Analysis per cycle33.3%33.3%
EUR – Analysis per oocyte/embryo113 (40.4%)142 (30.8%)
Change in weight and and oocyte/embryo characteristics according to invertion or control group.

Analysis of pregnancy and neonatal outcomes revealed no statistically significant differences although live birth rates trended higher in the intervention group due to a higher number of miscarriages among the control group.

LIFEstyle intervention
(n=51)
Control
(n=72)
Clinical pregnancy14 (27.5%)20 (27.8%)
Miscarriage1 (7.1%)7 (35.0%)
Live births13 (25.5%)13 (18.1%)
LGA2 (15.4%)5 (31.3%)
SGA1 (7.7%)0
Pregnancy and neonatal outcomes according to invertion or control group.

Similarly, LGA births was more prevalent in the control group but not statistically significant due to small study size.

Limitations

  1. Small study size.
  2. Not a true randomised comparison between groups.
  3. Duration of lifestyle intervention was potentially too short given the majority of women did not lose 5% of body weight.

Funding

This study was funded by ZonMw, the Dutch Organization for Health Research and Development.

Glossary

Blastocyst
A fertilised embryo that has developed an inner cell mass and outer layer (trophoblast) some time from day 4 onwards.

Morula stage
Early-stage embryo consisting of 16 cells prior to forming a blastocyst.

Neonate
Newborn child.

Oocyte
Unfertilised immature / mature egg.

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

Sonography
Ultrasound.

Similar studies

Einarsson S, et al. (2017). Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial. https://doi.org/10.1093/humrep/dex235

Mutsaerts M A, et al. (2016). Randomized Trial of a Lifestyle Program in Obese Infertile Women. https://doi.org/10.1056/nejmoa1505297

Leary C, et al. (2015). Human embryos from overweight and obese women display phenotypic and metabolic abnormalities. https://doi.org/10.1093/humrep/deu276

Luke B, et al. (2011). Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates. https://doi.org/10.1093/humrep/deq306


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