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Meta-Analysis
. 2022 Jul 1;5(7):e2222106.
doi: 10.1001/jamanetworkopen.2022.22106.

Association of Assisted Reproductive Technology With Offspring Growth and Adiposity From Infancy to Early Adulthood

Ahmed Elhakeem  1   2 , Amy E Taylor  1   2   3 , Hazel M Inskip  4   5 , Jonathan Huang  6   7 , Muriel Tafflet  8 , Johan L Vinther  9 , Federica Asta  10 , Jan S Erkamp  11   12 , Luigi Gagliardi  13 , Kathrin Guerlich  14 , Jane Halliday  15   16 , Margreet W Harskamp-van Ginkel  17 , Jian-Rong He  18 , Vincent W V Jaddoe  11   12 , Sharon Lewis  15   16 , Gillian M Maher  19   20 , Yannis Manios  21   22 , Toby Mansell  15   16 , Fergus P McCarthy  20   23 , Sheila W McDonald  24   25 , Emanuela Medda  26 , Lorenza Nisticò  26 , Angela Pinot de Moira  9 , Maja Popovic  27 , Irwin K M Reiss  12 , Carina Rodrigues  28   29 , Theodosia Salika  4 , Ash Smith  30 , Maria A Stazi  26 , Caroline Walker  30 , Muci Wu  24 , Bjørn O Åsvold  31   32   33 , Henrique Barros  28   29 , Sonia Brescianini  26 , David Burgner  15   34   35 , Jerry K Y Chan  7   36 , Marie-Aline Charles  8   37 , Johan G Eriksson  6   38   39   40 , Romy Gaillard  11   12 , Veit Grote  14 , Siri E Håberg  41 , Barbara Heude  8 , Berthold Koletzko  14 , Susan Morton  30 , George Moschonis  42 , Deirdre Murray  20   43 , Desmond O'Mahony  44 , Daniela Porta  10 , Xiu Qiu  18 , Lorenzo Richiardi  27 , Franca Rusconi  13 , Richard Saffery  15   16 , Suzanne C Tough  24   25 , Tanja G M Vrijkotte  17 , Scott M Nelson  3   45 , Anne-Marie Nybo Andersen  9 , Maria C Magnus  41 , Deborah A Lawlor  1   2   3 ; Assisted Reproductive Technology and Future Health (ART-Health) Cohort Collaboration
Affiliations
Meta-Analysis

Association of Assisted Reproductive Technology With Offspring Growth and Adiposity From Infancy to Early Adulthood

Ahmed Elhakeem et al. JAMA Netw Open. .

Abstract

Importance: People conceived using assisted reproductive technology (ART) make up an increasing proportion of the world's population.

Objective: To investigate the association of ART conception with offspring growth and adiposity from infancy to early adulthood in a large multicohort study.

Design, setting, and participants: This cohort study used a prespecified coordinated analysis across 26 European, Asia-Pacific, and North American population-based cohort studies that included people born between 1984 and 2018, with mean ages at assessment of growth and adiposity outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and February 2022.

Exposures: Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer) vs natural conception (NC; without any medically assisted reproduction).

Main outcomes and measures: The main outcomes were length / height, weight, and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13 age groups.

Results: Up to 158 066 offspring (4329 conceived by ART) were included in each age-group meta-analysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were NC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence, with differences largest at the youngest ages and attenuating with older child age. For example, adjusted mean differences in offspring weight were -0.27 (95% CI, -0.39 to -0.16) SD units at age younger than 3 months, -0.16 (95% CI, -0.22 to -0.09) SD units at age 17 to 23 months, -0.07 (95% CI, -0.10 to -0.04) SD units at age 6 to 9 years, and -0.02 (95% CI, -0.15 to 0.12) SD units at age 14 to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo transfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was -0.14 [95% CI, -0.20 to -0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, -0.15 to 0.15] SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat measurements, and there was imprecise evidence that offspring conceived by ART developed greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17 years: 0.23 [95% CI, -0.04 to 0.50] SD units).

Conclusions and relevance: These findings suggest that people conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Lewis reported receiving grants from Australian National Health and Medical Research Council during the conduct of the study. Dr McDonald reported receiving grants from University of Calgary during the conduct of the study. Dr Medda reported receiving grants from Italian Ministry of Health during the conduct of the study. Dr Nisticò reported receiving grants from Italian Ministry of Health and Chiesi Onlus Foundation during the conduct of the study. Dr Stazi reported receiving grants from Italian Ministry of Health during the conduct of the study. Dr Wu reported receiving grants from University of Calgary during the conduct of the study. Dr Brescianini reported receiving grants from Chiesi Onlus Foundation and Italian Ministry of Health during the conduct of the study. Dr Grote reported receiving grants from Commission of the European Community during the conduct of the study. Dr Håberg reported receiving grants from Norwegian Research Council during the conduct of the study. Dr Koletzko reported receiving personal fees from Annenberg, Baxter, Bayer, Barilla, Danone, Dairy Goat Cooperative, Dutch State Mines Nutritionals, Hipp, Nestle, and Reckitt Benckieser and grants from Danone, Nestle, and Dairy Goat Cooperative outside the submitted work. Dr Saffery reported receiving grants from National Health and Medical Research Council during the conduct of the study. Dr Vrijkotte reported receiving grants from the Amsterdam Academic Medical Centre, Amsterdam Public Health Services, and Dutch Organization for Health Research and Development during the conduct of the study. Dr Nelson reported receiving grants from Roche Diagnostics, Access Fertility, Modern Fertility, Ferring Pharmaceuticals, TFP Fertility, and Merck outside the submitted work Dr Magnus reported receiving grants from the Research Council of Norway during the conduct of the study. Dr Lawlor reported receiving grants from Medtronic and Roche Diagnostics during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Mean Difference in Length / Height, Weight, and Body Mass Index (BMI) Between Offspring Conceived via Assisted Reproductive Technology (ART) and Those Who Were Naturally Conceived (NC)
Cohort-specific results were adjusted for maternal age, parity, BMI (calculated as weight in kilograms divided by height in meters squared), smoking, education, ethnicity or country of birth, plus offspring sex and age. I2 represents the percentage of total variability that is due to between-cohort heterogeneity. Cohort-specific results are provided in eFigures 2-4 in the Supplement.
Figure 2.
Figure 2.. Mean Difference in Waist Circumference, Body Fat Percentage, and Fat Mass Index Between Offspring Conceived via Assisted Reproductive Technology (ART) and Those Who Were Naturally Conceived (NC)
Cohort-specific results were adjusted for maternal age, parity, body mass index, smoking, education, ethnicity/country of birth, plus offspring sex and age. I2 represents the percentage of total variability that is due to between-cohort heterogeneity. Cohort-specific results are provided in eFigures 5-7 in the Supplement.
Figure 3.
Figure 3.. Mean Difference in Growth and Adiposity Outcomes Between Offspring Conceived via Assisted Reproductive Technology (ART) and Those Who Were Naturally Conceived (NC), Separately for Offspring Who Were NC by Parents Who Were Subfertile or Fertile
Parents were classified as fertile if time to pregnancy within 12 months from when they began trying; parents were classified as subfertile if time to pregnancy was greater than 12 months. Cohort-specific results were adjusted for maternal age, parity, body mass index (BMI), smoking, education, ethnicity or country of birth, plus offspring sex and age.
Figure 4.
Figure 4.. Mean Difference in Growth and Adiposity Outcomes Between Offspring Conceived via Assisted Reproductive Technology (ART) and Those Who Were Naturally Conceived (NC), Separately for Offspring Conceived by Conventional In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI)
Cohort-specific results were adjusted for maternal age, parity, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), smoking, education, ethnicity or country of birth, plus offspring sex and age. The number of offspring at each age for the primary outcomes (length / height, weight, and BMI) varied from 1517 offspring conceived via conventional IVF, 1382 offspring conceived via ICSI, and 102 386 offspring who were NC for weight at age 3 to 5 months to 105 offspring conceived via conventional IVF, 37 offspring conceived via ICSI, and 11 164 offspring who were NC for BMI at age 14 to 17 years.
Figure 5.
Figure 5.. Mean Difference in Length / Height, Weight, and Body Mass Index (BMI) Between Offspring Conceived via Assisted Reproductive Technology (ART) and Those Who Were Naturally Conceived (NC), Separately for Offspring Conceived Using Fresh Embryo Transfer (ET) and Frozen-Thawed Embryo Transfer (FET)
Cohort-specific results were adjusted for maternal age, parity, BMI (calculated as weight in kilograms divided by height in meters squared), smoking, education, ethnicity or country of birth, plus offspring sex and age The number of offspring at each age varied from 1904 offspring conceived by fresh ET, 303 offspring conceived by FET, and 78 128 offspring who were NC for weight at age 3 to 5 months to 433 offspring conceived by fresh ET, 84 offspring conceived by FET, and 15 490 offspring who were NC for BMI at age 17 to 23 months.
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References

    1. Zegers-Hochschild F, Adamson GD, Dyer S, et al. . The International Glossary on Infertility and Fertility Care, 2017. Hum Reprod. 2017;32(9):1786-1801. doi:10.1093/humrep/dex234 - DOI - PMC - PubMed
    1. Crawford GE, Ledger WL. In vitro fertilisation/intracytoplasmic sperm injection beyond 2020. BJOG. 2019;126(2):237-243. doi:10.1111/1471-0528.15526 - DOI - PubMed
    1. Wang H, Abbas KM, Abbasifard M, et al. ; GBD 2019 Demographics Collaborators . Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1160-1203. doi:10.1016/S0140-6736(20)30977-6 - DOI - PMC - PubMed
    1. Levine H, Jørgensen N, Martino-Andrade A, et al. . Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum Reprod Update. 2017;23(6):646-659. doi:10.1093/humupd/dmx022 - DOI - PMC - PubMed
    1. Smith ADAC, Tilling K, Nelson SM, Lawlor DA. Live-birth rate associated with repeat in vitro fertilization treatment cycles. JAMA. 2015;314(24):2654-2662. doi:10.1001/jama.2015.17296 - DOI - PMC - PubMed

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