This retrospective case-control study is the first to compare pregnancy and live birth rates in gestational carriers vs. the “generally infertile.”

Study Background

WHAT

• Does Body Mass Index (BMI) impact the success of an IVF cycle in a gestational carrier?

WHY

• Increasing numbers of gestational carriers carrying IVF babies

• Global pandemic of obesity (per the CDC and the WHO, defined as BMI > 29.9)

• Higher BMI = higher risks of negative outcomes to mother and baby

• Higher BMI = unknown risks to IVF processes

WHERE

• IVF completed at a private fertility center in Toronto, Ontario, Canada

• Pregnancy information located in “Better Outcomes Registry & Network” (BORN) database

WHEN

• 2003-2016

WHO

• Gestational Carriers as test group and generally infertile as control group

  • N = 188 in each group

  • No age exclusions

  • Diagnosis exclusions were repeat implantation failure, repeat pregnancy loss, or thin endometrium before embryo transfer

  • Pre-transfer luteal support was “similar” for all cycles per an unspecified clinic protocol

HOW

• 1:1 gestational carrier to control match by BMI and treatment year

• Retrospective review

  • clinical charts on medical history

  • patient self-reported lifestyle factors

  • pregnancy outcomes

    • 2003-2008, directly contacted patients about birth information

    • 2009 onwards, searched BORN database

• Defined primary outcomes - clinical pregnancy, life birth, miscarriage rates

• Defined secondary outcomes - pregnancy complications

• Extensive statistics

  • utilized G*power program (version not stated)

  • alpha of 0.05, Beta of 0.80 and one degree of freedom

  • sufficient power from 65-126 cycles in each group

    Results

• BMI did not affect pregnancy, miscarriages, or live births

• More gestational carriers became pregnant and gave birth in normal, overweight, and obese groups; no statistically significant differences in morbidly obese

• No statistically significant differences in miscarriage rates (after Holm-Bonferroni correction to lower risk of false positive results)

• No statistically significant difference in pre-transfer endometrial thickness

• No statistically significant differences in embryo characteristics (quality, quantity, day of transfer)

Authors’ Thoughts

• Expected gestational carriers to be younger with more favorable birth records (why selected as carriers), higher pregnancy and birth rates consistent with prior studies

• Study strengths:

  • Increased ability to detect statistical differences by testing outcomes (pregnancy, birth, etc.) as both continuous and as binary variables

  • By using Holm-Bonferroni method to look at multiple hypotheses, eliminated the falsely positive difference detected in miscarriage rates.

• Study limitations:

  • small sample size

  • one fertility center

• Study results do not clarify if obesity affects results of IVF treatments

This Pharmacist’s Thoughts

• Differences at baseline, all statistically significant (p < 0.05)

  • Gestational carriers younger than controls (age 31.8 years vs. 37.3 years)

  • Age of source of oocytes (eggs) younger in gestational carriers than controls (age 28.6 years vs. 33.7 years)

  • Gestational carriers had more previous pregnancies and deliveries

  • Gestational carriers reported taking more psychiatric medications (16.0% vs. 6.2%)

  • Generally infertile controls reported lifestyles less conducive to pregnancy

    • 18.6% reported lack of exercise vs. 3.1% of gestational carriers

    • 5.6% report current recreational drug use vs. 1.1% of gestational carriers

• Since BMI does not distinguish the density of muscle mass, is BMI the optimal measurement to capture and measure the obesity in this population?

• Would different embryo protocols make a difference?

  • More gestational carriers transferred Day 5 embryos, more controls transferred Day 3 embryos

  • Primarily fresh embryo transfer (~90%), would there be detectable differences in a large study using primarily frozen embryos?

• Was all data reliably located? Contacting patients directly for 2003-2008 outcomes introduces risk of recall bias + introduces inconsistencies in data collection over entire study period

• The study did not note patient race or ethnicity data- are there subgroups where the outcomes may be different based on these demographics?

Conclusions

The study results should not lead to changes in selecting gestational carriers. A prospective multi-site study, with women closely matched between groups, would bolster the results of this study.

Currently, ASRM does not recommend excluding women from being gestational carriers based on BMI alone. Given that BMI might not be the best predictor of negative outcomes associated with obesity, future studies should include alternative markers of obesity, such as waist circumference or % body fat.

Resources

Abramowitz MK, Hall CB, Amodu A, Sharma D, Androga L, Hawkins M. Muscle mass, BMI, and mortality among adults in the United States: A population-based cohort study [published correction appears in PLoS One. 2018 May 24;13(5):e0198318]. PLoS One. 2018;13(4):e0194697. Published 2018 Apr 11. doi:10.1371/journal.pone.0194697

Adult Overweight and Obesity. Centers for Disease Control and Prevention website. https://www.cdc.gov/obesity/adult/index.html. Accessed August 25, 2020

Body Mass Index (BMI). Centers for Disease Control and Prevention website. https://www.cdc.gov/healthyweight/assessing/bmi/index.html. Accessed August 25, 2020.

Fuchs Weizman N, Defer MK, Montbriand J, Pasquale JM, Silver A, Librach CL. Does body mass index impact assisted reproductive technology treatment outcomes in gestational carriers. Reprod Biol Endocrinol. 2020;18(1):35. Published 2020 May 2. doi:10.1186/s12958-020-00602-2

Gestational Carrier (Surrogate). American Society for Reproductive Medicine. https://www.reproductivefacts.org/news-and-publications/patient-fact-sheets-and-booklets/documents/fact-sheets-and-info-booklets/gestational-carrier-surrogate/ Accessed August 25, 2020.

Made in Boise. https://www.pbs.org/independentlens/films/made-in-boise/. Accessed August 25, 2020.

Practice Committee of the American Society for Reproductive Medicine and Practice Committee of the Society for Assisted Reproductive Technology. Electronic address: ASRM@asrm.org; Practice Committee of the American Society for Reproductive Medicine and Practice Committee of the Society for Assisted Reproductive Technology. Recommendations for practices utilizing gestational carriers: a committee opinion. Fertil Steril. 2017;107(2):e3-e10. doi:10.1016/j.fertnstert.2016.11.007