Current knowledge of obesity's effects in the pre- and periconceptional periods and avenues for future research

doi:10.1016/j.ajog.2010.06.043

American Journal of Obstetrics and Gynecology

Volume 203, Issue 6, December 2010, Pages 525-530

https://doi.org/10.1016/j.ajog.2010.06.043 Get rights and content

The prevalence of obesity is growing among reproductive-age women. This is concerning because obesity has significant health-related consequences. Aside from the long-term risks of diabetes, heart disease, and some types of cancer, obesity poses immediate threats for young women including subfertility and adverse early and late pregnancy outcomes. Epidemiologic and experimental studies demonstrate associations between prepregnancy obesity and poor reproductive outcomes; however, the mechanisms involved are poorly understood. We discuss current knowledge of the pathophysiology of obesity in early reproductive events and how these events may affect reproductive outcomes including fertility and miscarriage risk. We also discuss avenues for future research and interventions to improve reproductive outcomes for obese women.

Section snippets

Obesity and ovulation

Increased incidence of subfertility among obese women may be attributed in part to the frequent cooccurrence of obesity with polycystic ovary syndrome (PCOS),²⁰ a relatively common condition characterized by hyperandrogenism and anovulation and associated with insulin resistance.21, 22 PCOS is not uncommon in women of normal weight; however, in obese women insulin resistance may lead to clinical features consistent with PCOS.23, 24

Insulin resistance and hyperinsulinemia consequent of obesity

Obesity and the oocyte

Insight into the importance of maternal physiology on oocyte quality can be demonstrated in experimental animal models of maternal diabetes in which there is an increase in granulosa cell apoptosis of the ovarian follicle and impaired oocyte maturation.15, 16, 38 Similar to diabetes, obesity is a condition marked by aberrations in circulating levels of substrates for energy production, and it too appears to have effects on oocyte quality. Visually, these effects appear to be primarily on oocyte

Obesity and the embryo

Embryo quality is affected by poor oocyte quality, and this may be an issue for obese women. This has been documented clinically in obese women undergoing IVF in which embryos derived from oocytes fertilized in vitro are of poorer quality than those derived from normal-weight women.48, 57 On the other hand, IVF studies investigating embryo quality in obese women are conflicting, and their findings on embryo quality may not reflect what truly happens in spontaneous conceptions.⁵⁸

Another issue to

Obesity and early pregnancy

In addition to increased risks of congenital anomalies, preeclampsia, gestational diabetes, and stillbirth among obese pregnant women,8, 9, 66, 67, 68 there are also data to suggest risk of miscarriage is increased among obese women.⁶⁹ This association is difficult to study, however, because many spontaneously pregnant women are not followed up closely in early pregnancy and may not ever present for care if they experience a miscarriage. Women undergoing infertility treatment may offer more

Limitations of current evidence and future avenues for research

The bulk of the current data available investigating relationships between obesity and oocytes and early reproduction in spontaneous conception is restricted to work in animal models and a small amount of clinical data from obese women undergoing IVF (Table 2). Unfortunately, the available clinical data are limited in that most women undergoing IVF are treated with gonadotropins. Drug regimens and protocols and response to drugs may vary from patient to patient, with many obese women requiring

References (78)

M. Metwally et al.
Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception?A meta-analysis of the evidence
Fertil Steril
(2008)
P.M. Catalano et al.
Perinatal risk factors for childhood obesity and metabolic dysregulation
Am J Clin Nutr
(2009)
R.J. Norman et al.
Effects of obesity on assisted reproductive technology outcomes
Fertil Steril
(2008)
R. Azziz et al.
The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report
Fertil Steril
(2009)
B.O. Yildiz et al.
Ovarian and adipose tissue dysfunction in polycystic ovary syndrome: report of the 4th special scientific meeting of the Androgen Excess and PCOS Society
Fertil Steril
(2010)
R.J. Chang
Polycystic ovary syndrome and hyperandtrogenic states
R.J. Norman et al.
Polycystic ovary syndrome
Lancet
(2007)
K.D. Helm et al.
Physiologic and pathophysiologic alternations of the neuroendocrine components of the reproductive axis
R.M. Fenichel et al.
Leptin levels and luteinizing hormone pulsatility in normal cycling women and their relationship to daily changes in metabolic rate
Fertil Steril
(2008)
S. Moschos et al.
Leptin and reproduction: a review
Fertil Steril
(2002)

R.L. Robker

Evidence that obesity alters the quality of oocytes and embryos

Pathophysiology

(2008)

D.T. Carrell et al.

Body mass index is inversely related to intrafollicular HCG concentrations, embryo quality and IVF outcome

Reprod Biomed Online

(2001)

I.S.R. Obeso et al.

The impact of body mass index (BMI) on ovarian stimulation in young oocyte donors

Fertil Steril

(2009)

E.S. Jungheim et al.

Morbid obesity is associated with lower clinical pregnancy rates after in vitro fertilization in women with polycystic ovary syndrome

Fertil Steril

(2009)

M. Metwally et al.

Effect of increased body mass index on oocyte and embryo quality in IVF patients

Reprod Biomed Online

(2007)

J. Bellver et al.

Female obesity impairs in vitro fertilization outcome without affecting embryo quality

Fertil Steril

(2010)

A.O. Hammoud et al.

Impact of male obesity on infertility: a critical review of the current literature

Fertil Steril

(2008)

J.L. Weiss et al.

Obesity, obstetric complications and cesarean delivery rate—a population-based screening study

Am J Obstet Gynecol

(2004)

A. Vahratian

Prevalence of overweight and obesity among women of childbearing age: results from the 2002 National Survey of Family Growth

Matern Child Health J

(2009)

K.M. Flegal et al.

Cause-specific excess deaths associated with underweight, overweight, and obesity

JAMA

(2007)

D.C. Gesink Law et al.

Obesity and time to pregnancy

Hum Reprod

(2007)

C.H. Ramlau-Hansen et al.

Subfecundity in overweight and obese couples

Hum Reprod

(2007)

L.A. Wise et al.

An internet-based prospective study of body size and time to pregnancy

Hum Reprod

(2010)

T.E. O'Brien et al.

Maternal body mass index and the risk of preeclampsia: a systematic overview

Epidemiology

(2003)

A. Dokras et al.

Obstetric outcomes after in vitro fertilization in obese and morbidly obese women

Obstet Gynecol

(2006)

K.J. Stothard et al.

Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and meta-analysis

JAMA

(2009)

G.Q. Chang et al.

Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity

J Neurosci

(2008)

E.A. Nohr et al.

Severe obesity in young women and reproductive health: the Danish National Birth Cohort

PLoS One

(2009)

P.M. Catalano et al.

Fetuses of obese mothers develop insulin resistance in utero

Diabetes Care

(2009)

M.E. Symonds et al.

Nutritional programming of the metabolic syndrome

Nat Rev Endocrinol

(2009)

A.S. Chang et al.

Maternal diabetes adversely affects preovulatory oocyte maturation, development, and granulosa cell apoptosis

Endocrinology

(2005)

E.S. Jungheim et al.

The impact of type 1 and type 2 diabetes mellitus on the oocyte and the preimplantation embryo

Semin Reprod Med

(2008)

A. Wyman et al.

One-cell zygote transfer from diabetic to nondiabetic mouse results in congenital malformations and growth retardation in offspring

Endocrinology

(2008)

R. Artal et al.

Weight gain recommendations in pregnancy and the obesity epidemic

Obstet Gynecol

(2010)

F. Alvarez-Blasco et al.

Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women

Arch Intern Med

(2006)

Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome

Fertil Steril

(2004)

J.E. Nestler

Obesity, insulin, sex steroids and ovulation

Int J Obes Relat Metab Disord

(2000)

N. Santoro et al.

Body size and ethnicity are associated with menstrual cycle alterations in women in the early menopausal transition: the Study of Women's Health across the Nation (SWAN) daily hormone study

J Clin Endocrinol Metab

(2004)

Rachon D, Teede H. Ovarian function and obesity—interrelationship, impact on women's reproductive lifespan and...

Cited by (145)

Neighborhood disadvantage is associated with decreased ovarian reserve in women with overweight and obesity
2023, Fertility and Sterility
To evaluate the association between neighborhood disadvantage and ovarian reserve stratified by body mass index (BMI).
Cross-sectional cohort study.
Single academic medical center.
A total of 193 healthy reproductive-age women with regular menstrual cycles in the St. Louis, Missouri metropolitan area.
Residence in a disadvantaged neighborhood.
Ovarian reserve as assessed by ovarian antral follicle count (AFC) and serum anti-Müllerian hormone (AMH) concentration.
Women (n = 193) ranged from 20 to 44 years. The majority had overweight or obesity (59%, n = 117) with mean BMI of 28±7 kg/m². Forty-eight women lived in the most disadvantaged neighborhood quartile, of which 75% had overweight or obesity, compared with 54% of the 145 women living in the 3 less disadvantaged neighborhood quartiles. When controlling for age, race, and smoking status, women with overweight or obesity living in the most disadvantaged neighborhoods had significantly lower AMH compared with those living in the less disadvantaged neighborhoods. Antral follicle count did not differ among women with overweight or obesity by neighborhood of residence. Neighborhood disadvantage was not associated with ovarian reserve by AFC or AMH in women with normal weight or underweight status.
Living in a socioeconomically deprived area is associated with lower markers of ovarian reserve among women with an elevated BMI.
La desventaja del vecindario está asociada a disminución de la reserva ovárica en mujeres con sobrepeso y obesidad.
Evaluar la asociación entre la desventaja del vecindario y la reserva ovárica estratificada por el índice de masa corporal (IMC).
Estudio transversal de cohorte.
Centro médico académico único.
Un total de 193 mujeres sanas en edad reproductiva con ciclos menstruales regulares en la zona metropolitana de St. Louis, Missouri.
Residencia en un vecindario desfavorecido.
Reserva ovárica evaluada mediante la cuenta de folículos antrales (CFA) y la concentración sérica de hormona antimulleriana (HAM).
Mujeres (n=193) entre 20 a 44 años. La mayoría con sobrepeso u obesidad (59%, n=117) con IMC medio de 28.7 kg/m2. Cuarenta y ocho mujeres vivían en el cuartil de vecindario mas desfavorecido, de las cuales 75% tenían sobrepeso u obesidad, en comparación con 54% de las 145 mujeres que vivían en los 3 cuartiles menos desfavorecidos. Al controlar para edad, raza y tabaquismo, las mujeres con sobrepeso u obesidad viviendo en los vecindarios mas desfavorecidos tenían significativamente menor HAM en comparación con aquellas viviendo en los vecindarios menos desfavorecidos. La cuenta de folículos antrales no difirió entre las mujeres con sobrepeso u obesidad de acuerdo al vecindario de residencia. La desventaja del vecindario no se asoció con la reserva ovárica por CFA ni HAM en mujeres con peso normal o bajo peso.
Vivir en áreas socioeconómicamente deprivadas se asocia con marcadores más bajos de reserva ovárica en mujeres con IMC elevado.
Metabolic risk factors and fertility disorders: A narrative review of the female perspective
2022, Reproductive Biomedicine and Society Online
Metabolic risk factors such as obesity are considered major obstacles to female fertility. Chronic infertility imposes psychological and social burdens on women because infertility violates societal gender roles. Although the prevalence of obesity among women is expected to increase in the future, the relevance of metabolic status for fertility is still underestimated. However, the assessment of metabolic risk factors is highly relevant for understanding fertility disorders and improving infertility treatment. This narrative review discusses the associations of metabolic risk factors (e.g. obesity, female athlete triad, oxidative stress) with significant infertility. An electronic search was conducted for studies published between 2006 and 2020 in Cumulative Index to Nursing and Allied Health Literature, ScienceDirect, PubMed, Scopus, Google Scholar and related databases. In total, this search identified 19,309 results for polycystic ovary syndrome, 28,969 results for endometriosis, and only 1611 results for idiopathic and/or unknown infertility. For the present narrative review, 50 relevant studies were included: 19 studies were on obesity, 24 studies investigated the female athlete triad, and seven studies addressed other risk factors, including reactive oxygen species. This narrative review confirms the direct impact of obesity on female infertility, while the effect of other risk factors needs to be confirmed by large-scale population studies.
Polycystic Ovary Syndrome and Irritable Bowel Syndrome: Is There a Common Pathway?
2024, Endocrinology, Diabetes and Metabolism
Preconception Diet Interventions in Obese Outbred Mice and the Impact on Female Offspring Metabolic Health and Oocyte Quality
2024, International Journal of Molecular Sciences
Association between adverse nutrition status by BMI and increased time-to-pregnancy in planed pregnancy couples: A cohort study in Guangzhou, China
2024, Research Square
Obesity and Miscarriage
2024, Seminars in Reproductive Medicine

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: E.S.J. receives support through the Women's Reproductive Health Research Career Development Program of the National Institutes of Health (K12HD063086-01).

: Reprints not available from the authors.

View full text

ReviewCurrent knowledge of obesity's effects in the pre- and periconceptional periods and avenues for future research

Section snippets

Obesity and ovulation

Obesity and the oocyte

Obesity and the embryo

Obesity and early pregnancy

Limitations of current evidence and future avenues for research

Fertil Steril

Am J Clin Nutr

Fertil Steril

Fertil Steril

Fertil Steril

Lancet

Fertil Steril

Fertil Steril

Pathophysiology

Reprod Biomed Online

Fertil Steril

Fertil Steril

Reprod Biomed Online

Fertil Steril

Fertil Steril

Am J Obstet Gynecol

Prevalence of overweight and obesity among women of childbearing age: results from the 2002 National Survey of Family Growth

Matern Child Health J

Cause-specific excess deaths associated with underweight, overweight, and obesity

JAMA

Obesity and time to pregnancy

Hum Reprod

Subfecundity in overweight and obese couples

Hum Reprod

An internet-based prospective study of body size and time to pregnancy

Hum Reprod

Maternal body mass index and the risk of preeclampsia: a systematic overview

Epidemiology

Obstetric outcomes after in vitro fertilization in obese and morbidly obese women

Obstet Gynecol

Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and meta-analysis

JAMA

Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity

J Neurosci

Severe obesity in young women and reproductive health: the Danish National Birth Cohort

PLoS One

Fetuses of obese mothers develop insulin resistance in utero

Diabetes Care

Nutritional programming of the metabolic syndrome

Nat Rev Endocrinol

Maternal diabetes adversely affects preovulatory oocyte maturation, development, and granulosa cell apoptosis

Endocrinology

The impact of type 1 and type 2 diabetes mellitus on the oocyte and the preimplantation embryo

Semin Reprod Med

One-cell zygote transfer from diabetic to nondiabetic mouse results in congenital malformations and growth retardation in offspring

Endocrinology

Weight gain recommendations in pregnancy and the obesity epidemic

Obstet Gynecol

Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women

Arch Intern Med

Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome

Fertil Steril

Obesity, insulin, sex steroids and ovulation

Int J Obes Relat Metab Disord

Body size and ethnicity are associated with menstrual cycle alterations in women in the early menopausal transition: the Study of Women's Health across the Nation (SWAN) daily hormone study

J Clin Endocrinol Metab

Review
Current knowledge of obesity's effects in the pre- and periconceptional periods and avenues for future research