The effect of obesity on fertility: A systematic review

Abstract

Objective

Obesity and female infertility are two rising public health issues. The relationship between them has been partially explored; however, systematic reviews summarizing the impact of obesity on female infertility are limited.

Materials and methods

We investigated the relationships between obesity and infertility outcomes in adult females, through a systematic review using PubMed and Scopus databases.

Results

Findings from 14 studies concluded that obese women (as defined by body mass index – BMI) and centrally obese women (as defined by waist circumference – WC) experienced prolonged time to pregnancy (TTP) and a gradually increased risk of infertility compared to women with normal values for these indicators. Among the three obesity indicators, WC followed by BMI appeared to increase infertility risk when values exceeded normal thresholds. The waist–hip ratio – WHR indicator, though less frequently studied, displayed variability in results regarding TTP. As for linearity, this was investigated only for WC and BMI, revealing non-linear relationships with infertility risk and TTP, respectively. The relationship between obesity and infertility outcome is presented as positive, particularly in the case of central obesity in women of reproductive age. Overweight women experience negative effects on fertility, though not at the extent that appear on obese women.

Conclusions

The present study highlights the need for maintaining a healthy, normal weight for better fertility outcomes. Further research to uncover the deeper mechanisms of obesity that cause reproductive problems in women and their connection with various obesity indicators is encouraged.

Resumen

Objetivo

La obesidad y la infertilidad femenina son dos problemas de salud pública en auge. Su relación se ha explorado parcialmente; sin embargo, las revisiones sistemáticas que resumen el impacto de la obesidad en la infertilidad femenina son limitadas.

Materiales y métodos

Se investigaron las relaciones entre la obesidad y los resultados de infertilidad en mujeres adultas mediante una revisión sistemática utilizando las bases de datos PubMed y Scopus.

Resultados

Los hallazgos de 14 estudios concluyeron que las mujeres obesas (definidas por el índice de masa corporal [IMC]) y las mujeres con obesidad central (definidas por la circunferencia de la cintura [CC]) experimentaron un tiempo hasta el embarazo (TTP) prolongado y un riesgo de infertilidad gradualmente mayor en comparación con las mujeres con valores normales para estos indicadores. Entre los tres indicadores de obesidad, el CC, seguido del IMC, pareció aumentar el riesgo de infertilidad cuando los valores superaron los umbrales normales. El indicador del índice cintura-cadera (CCC), aunque menos estudiado, mostró variabilidad en los resultados con respecto al TTP. En cuanto a la linealidad, esta se investigó únicamente para la CC y el IMC, revelando relaciones no lineales con el riesgo de infertilidad y el TTP, respectivamente. La relación entre la obesidad y los resultados de infertilidad se presenta como positiva, especialmente en el caso de la obesidad central en mujeres en edad reproductiva. Las mujeres con sobrepeso experimentan efectos negativos en la fertilidad, aunque no en la misma medida que se observan en las mujeres obesas.

Conclusiones

El presente estudio destaca la necesidad de mantener un peso saludable y normal para obtener mejores resultados de fertilidad. Se recomienda realizar más investigaciones para descubrir los mecanismos más profundos de la obesidad que causan problemas reproductivos en las mujeres y su conexión con diversos indicadores de obesidad.

Introduction

Based on the World Health Organization (WHO), 43% of the adult population worldwide is overweight, while 16% are obese, a percentage that corresponds to 890 million people and thus, the prevalence of obesity has more than doubled since 1990 for adults.¹ Overall, the prevalence of obesity has been increasing over the years, regardless the age, gender, nationality, socioeconomic status, and geographic location.²

Infertility is defined as the inability to achieve pregnancy after at least 12 months of regular, unprotected sexual intercourse.³ Often, the term “subfertility” is used interchangeably with “infertility” when unsuccessful attempts to conceive exceed 12 months. Infertility can be classified as primary or secondary. Primary infertility refers to individuals who have never achieved a pregnancy, while secondary infertility is defined as the inability to conceive after at least one previous successful pregnancy.⁴ The WHO estimates that about 50–80 million women worldwide experience infertility⁵ and, as a result, these women may experience more psychological distress, stress, social rejection, stigma, and/or violence. It is estimated that 1 in 6 people globally experience infertility issues in their lifetime, a percentage that exceeds 15%.⁶

Recently there's been a great research interest about the relationship between obesity and infertility. Previous studies have been conducted aiming to examine the relationship between obesity and female infertility. A systematic review by Pourghazi et al.⁷ concluded that adolescent obesity is associated with having fewer children in the future for both sexes and that higher body mass index (BMI) in young women may increase the risk of reproductive cycle problems. Also, the systematic review by Zhou et al.⁸ showed an increased likelihood of prolonged TTP in overweight and obese women compared to women with normal weight prior to conception, as well as an increased likelihood of infertility. Moreover, the group of underweight women also showed an increased likelihood of prolonged TTP, reinforcing the relationship between BMI and women's reproductive health.

The relationship between body weight and issues in the female reproductive system is positive, as obese women tend to have higher failure rates in assisted reproductive techniques and lower conception rates and require more time to achieve a successful pregnancy compared to non-obese women.⁹ The relationship between obesity and infertility is not entirely clear, as this connection appears to be multifactorial, with some mechanisms still under investigation.¹⁰ Maintaining a normal weight for the preservation of female reproductive functions is scientifically supported, as approximately 1 in 5 cases of infertility is due to unhealthy body weight.¹¹ A recent report from the Practice Committee of the American Society for Reproductive Medicine concludes that there is no scientific evidence supporting the implementation of policies for providing infertility treatments in overweight/obese women.¹² Thus, the main objective of this study was to examine the association between infertility and obesity among women of reproductive age.

Methods

Search strategy

PubMed and Scopus databases were searched for studies published between 2014 and 2025 examining the association between infertility and obesity among women of reproductive age. The search strategy followed a matrix combination approach as shown in Table 1. In addition, the reference lists of the selected articles were manually searched to identify additional studies. The searches were conducted independently by two researchers (ME and SC). Conflicting assessments were resolved via discussion until a consensus was achieved.

Table 1.

Results of search strategy in PubMed and Scopus.

	Keywords PubMed	Number of search	Number of retrieved studies	Keywords Scopus	Number of search	Number of retrieved studies
Exposure – obesity	(obese[Title] OR obesity[Title] OR overweight[Title] OR “body mass index”[Title] OR BMI[Title] OR “waist-to-hip”[Title] OR adiposity[Title] OR “excess weight”[Title] OR “waist circumference”[Title] OR “prepregnancy weight”[Title] OR “preconception weight”[Title] OR pre-pregnancy[Title] OR pre-conception[Title] OR “body fat”[Title])	#1	209,360	obese OR obesity OR overweight OR “body mass index” OR BMI OR waist-to-hip OR adiposity OR “excess weight” OR “waist circumference” OR “prepregnancy weight” OR “preconception weight” OR pre-pregnancy OR pre-conception OR “body fat”)	#1	248,842
Outcome – infertility	(fertility[Title] OR infertility[Title] OR “infertility risk”[Title] OR “infertility ratio”[Title] OR time-to-pregnancy[Title] OR “time to pregnancy” OR “time to conceive”[Title] OR time-to-conceive)	#2	48,399	TITLE (fertility OR infertility OR “infertility risk” OR “infertility ratio” OR time-to-pregnancy OR “time to pregnancy” OR “time to conceive” OR time-to-conceive)	#2	75,090
Methodology type	NOT review[Publication Type]	#3	3,421,978	–	–	–
#1 AND #2 AND #3		#4	324	#1 AND #2	#3	435
#4 and Additional Filters: English, Humans, Female, Adult: 19+ years, from 2014 to 2024		#5	71	# 3 and Additional Filters: PUBYEAR > 2013 AND PUBYEAR < 2025 AND NOT ((DOCTYPE,“re”)) AND ((DOCTYPE,“ar”))AND PUBYEAR > 2013 AND PUBYEAR < 2025 AND (LIMIT-TO (DOCTYPE,“ar”)) AND (LIMIT-TO (LANGUAGE,“English”)) AND (LIMIT-TO (EXACTKEYWORD,“Human”) OR LIMIT-TO (EXACTKEYWORD,“Article”) OR LIMIT-TO (EXACTKEYWORD,“Female”) OR LIMIT-TO (EXACTKEYWORD,“Adult”))	#4	188

All original articles including prospective and retrospective cohort studies and cross-sectional studies that were published between 2014 and 2025, including women of reproductive age (≥18 years old) were included. The exposure of interest was focused on three measured indexes, BMI, WC, and WHR, while the outcomes of interest were infertility as the definition given by WHO and TTP. Articles published in languages other than English, articles that did not meet the criteria for methodology type (not a cohort study or a cross-sectional study), exposure and/or outcome of interest, or the target population was out of the reproductive age range were excluded.

Study selection and data extraction

A two-step process was employed for selecting studies. Initially, two reviewers (ME and SC) independently screened the titles and abstracts identified through the initial searches. Full-text manuscripts were retrieved for all citations that appeared to meet the predefined selection criteria. In the second stage, the final decision of inclusion or exclusion was determined after a thorough review of the full texts of the eligible articles. Any disagreements regarding inclusion were resolved through consensus with a third reviewer (MK).

Data extraction was carried out by two reviewers (ME and SC), who documented the following details from each eligible study: first author, year of publication, country, study design, sample size, type of intervention, intervention duration, follow-up period, and key outcome measures. Any discrepancies were resolved through discussion with a third reviewer (MK).

Assessment of methodological quality and data synthesis

Two independent reviewers (ME and SC) completed the quality assessment of the included studies. For cohort studies, the Newcastle–Ottawa scale was used based on its selection, exposure, and comparability variables.¹³ The Newcastle–Ottawa quality assessment scale adapted for cross-sectional studies was used for the methodological quality of the included cross-sectional studies.¹⁴ Any disagreements were resolved through discussions with the third reviewer (MK). Due to significant variability among the studies in terms of outcome measures and assessment tools, a formal meta-analysis was not conducted. Instead, all included studies were summarized descriptively, and a qualitative synthesis was performed.

Results

The flowchart for the literature search is presented in Fig. 1. Overall, fourteen studies were deemed eligible for inclusion in the current study. Six were cross-sectional^15–20 and eight were cohort studies.^21–28 Among the cohort studies, 5 were prospective studies,^{21,22,24,27,28} while 3 were retrospective studies.^23,25,26

Figure 1.

Flowchart for the final inclusion of articles of the systematic review.

Baseline demographic/clinical characteristics

A total of 2,409,497 women aged 18–49 from several countries were included in the study, with the United States being the most frequently included country (N = 5). The BMI ranged between 18.5 and 45 kg/m², the WC between 56.4 and 178 cm and the WHR from <0.75 to ≥0.85. Furthermore, the average duration of follow-up of prospective cohort studies was more than 12 months.

Assessment of methodological quality of studies

Tables 2 and 3 present the results of the quality assessment for cross-sectional and cohort studies, respectively, using the relative Newcastle–Ottawa scale tool. Overall, 11 out of the 14 studies in the systematic review have been assessed with high methodological quality, 2 had moderate quality, and only 1 study was assessed with a low methodological quality.

Table 2.

Results of methodological quality assessment for cross-sectional studies.

Study	Selection	Comparability	Outcome	Score
Dhandapani, Kodavanji and Vinodini, 2016	****	–	**	6/10
Zhu et al., 2022	****	**	**	8/10
Tang et al., 2023	*****	**	*	8/10
Yin et al., 2023	*****	**	*	8/10
Ke, Feng and Chen, 2023	*****	**	*	8/10
Wang et al., 2024	***	**	*	6/10

Abbreviations: >7 = high, 5–6 = moderate, 0–4 = low methodological quality.

Table 3.

Results of methodological quality assessment for cohort studies.

Study	Selection	Comparability	Outcome	Score
McKinnon et al., 2016	***	**	**	7/9
Loy et al., 2018	***	**	**	7/9
Mena, Mielke and Brown, 2020	***	**	**	7/9
Zhang et al., 2020	****	**	*	7/9
Fang et al., 2020	***	**	**	7/9
Hernaez et al., 2021	**	**	*	5/9
Boxem at al., 2024	***	**	**	7/9
Zhang et al., 2024	****	**	**	8/9

Abbreviations: >7 = high, 5–6 = moderate, 0–4 = low methodological quality.

Results from cross-sectional studies

In the cross-sectional study by Dhandapani et al.,¹⁵ the aim was to examine the association between BMI with primary and secondary infertility rates. The study demonstrated that overweight women had higher percentage of primary infertility (45.3%) than obese women (5.8%), while obese women exhibited a higher rate of secondary infertility compared to primary infertility (10.4%). Another study found a nonlinear relationship between BMI and infertility, with the risk of infertility increasing at unnormal BMI values. A positive correlation of 3% was shown at BMI values ≥19.5 kg/m² (p < 0.0001). In an adjusted model for confounding factors, the likelihood of infertility for obese women (BMI >29.9 kg/m²) reached 74% (p < 0.0004) compared to women with a normal BMI (BMI = 18.5–24.9 kg/m²).¹⁶ The cross-sectional study by Tang et al.¹⁸ indicated a 2% increased risk per unit rise in WC (p < 0.001), and specifically, an 118% increased risk of infertility for obese women (p < 0.001). Obesity-related BMI values showed nearly double the risk of infertility (183%) (p < 0.05). The study by Yin et al.¹⁹ showed that the likelihood of infertility increased by 121% for women with higher WC compared to women with lower WC and the risk increased by 2% per unit rise in WC (p < 0.01). Furthermore, the non-linearity of the relationship was statistically significant for WC values <116.6 cm, where an increase in WC was associated with an increased risk of infertility. The study by Ke et al.¹⁷ found a positive relationship between WC and infertility, as for every cm increase in WC, the risk increased by 3% (p < 0.01). The 5th quintile had a 264% higher risk of infertility compared to the 1st quintile (p < 0.05). In the study by Wang et al.,²⁰ although the percentage of overweight/obese and centrally obese women was higher in the infertile group, which contributed to an increased risk of infertility compared to women with normal body types, the relationship between these variables was not statistically significant (see Table 4).

Table 4.

Main characteristics of the included studies.

Study	Type of study/country	Participants/acceptance criteria	Exposure/outcome	Adjustments/confounding factors	Results	Conclusions
Dhandapani, Kodavanji and Vinodini, 2016	Cross-sectional, India	204 women with infertility (WHO criteria), 18–40 years old who were hospitalized in a tertiary care hospital	BMI (WHO criteria)Primary + Secondary Infertility (WHO criteria). Collection of medical reports	N/A	Primary infertility: overweight 45.3%, obese 5.8%Secondary infertility: overweight 37.3%, obese 10.4%, normal-weight women 44.8%.	Deviation from normal weight, either upward or downward, can lead to primary infertility and, secondarily, to secondary infertility.
McKinnon et al., 2016	Prospective,USA,Canada	2062 women aged 21–45 from PRESTO 2013–2016 in a stable relationship, trying to conceive without the use of contraception or assisted reproduction techniques, and not pregnant at the start of the study.	BMI: WHO criteria, WHR + WC: adjustments based on sampleTTP:Questionnaires: total number of menstrual cycles attempted for conception before the start of the study, average menstrual cycle length, date of the last menstrual cycle before the study's start, and dates of menstrual cycles recorded in all questionnaires	Nationality, education, income, number of births, smoking history, alcohol consumption, frequency of sexual intercourse, methods to improve conception chances, last contraceptive method, partner's age/height/weight.Association BMI + FR: + physical exerciseAssociation WHR/WC + FR: + physical exercise + BMI	Fecundability ratio (FR): BMI: 25–29.9, 30–34.9, 35–39.9, 40–44.9, and 45 kg/m^2 was 1.01, 0.98, 0.78, 0.61 and 0.42.WC: ≥90, 77–89 και 66–76 was 0.80, 1.02, 1.04 compared to <66 cm. WHR ≥0.85, 0.80–0.84 και 0.75–0.79 was 0.87, 0.94, 1.04Reduced fertility for BMI values ≥30 kg/m^2	Reduced fertility and delayed pregnancy (higher TTP) in women suffering from total or central obesity. Increased BMI values (≥30 kg/m^2), WHR, and WC lead to reduced fertility
Loy et al., 2018	Prospective, Singapore	477 women 18–45 years old S-PRESTO 2015–2017 Chinese, Malaysians, Indians, without type I or II diabetes, trying to conceive for <18 months, have not taken antiepileptic drugs, steroids, or undergone assisted reproductive technology procedures >1 month before enrolling in the study.	1. BMI, 2. WHR, 3. WC WHO criteriaTTP: (months of attempting conception before study enrollment/average menstrual cycle length) + [(date of last period before conception or during the last communication) − (date of last period at enrollment)]/average menstrual cycle length	Age, ethnicity, education, number of births, menstrual cycle length, WHR*, BMI*	Fecundability ratio (FR):ΔMΣ: FR = 0.66 (23–27.4), FR = 0.53 (≥27.5)WC: FR = 0.76 (75–80), FR = 0.88 (81–86) and FR = 0.74 (≥87)WHR: FR = 0.76 (0.80–0.84) και FR = 1.16 (≥0.85)	Higher BMI values are indicators of lower fertility, while factors such as WC and WHR were not associated with infertility.
Fang et al., 2020	Retrospective, China	50927 women 20–47 years old from NFPHEP who wanted to conceive	BMI: WGOC criteriaTTP: (interval between the enrollment date and the last menstrual period)Infertility defined as TTP >6 months	Age, household type, education, exposure to smoking, alcohol consumption, stress, age at menarche, menstrual cycle regularity, spontaneous miscarriage, induced abortion, number of pregnancies, number of births.	Fecundability odds ratio (FOR):overweight/obese (FOR = 0.96)Infertility odds ratio (OR): overweight/obese (OR = 1.08)Non-linear relationship between BMI and fecundability: negative relationship for BMI values >22 kg/m^2.	High BMI before pregnancy and prolonged TTP and infertility are correlated, and BMI independently affects fertility and the risk of sterility.
Mena, Mielke and Brown, 2020	Prospective, Australia	6130 women who participated from 2000 (ages 22–27) to 2015 (ALSWH).	BMI: WHO criteriaCumulative incidence of fertility problems (HR): “Have you ever experienced fertility problems with your partner?” (Failed attempt to conceive after ≥12 months of trying?)	Marital status, country of birth, area of residence, education level, alcohol consumption, smoking, physical activity levels, sitting time, and reproductive health indicators.	Cumulative incidence rate (HR): obese (HR = 1.36), overweight (HR = 1.18)Infertility Incidence (IR): normal/underweight (IR = 2.79), overweight (IR = 3.44), obese (IR = 4.09)	Positive correlation between high BMI and infertility problems
Zhang et al., 2020	Retrospective, China	2,302,782 women 20–49 years old, from NFPCP 2015–2017 without a previous pregnancy and with regular menstrual cycles, aiming to conceive	BMI: WGOC criteriaTTP:[Date of last period (pregnant) or date of last tracking (non-pregnant) − date of questionnaire initiation]/average menstrual cycle length +1	Age, ethnicity, education level, profession, area of residence, alcohol consumption, exposure to smoking, medical history and treatments, menstrual cycle information, height, weight, blood pressure.	Fecundability odds ratio (FOR): overweight (FOR = 0.95), obesity (FOR = 0.80)Non-linear relationship between FOR + BMI:Optimal BMI for lower TTP is between 20.61 and 23.06 kg/m^2	Abnormal BMI values before pregnancy can lead to prolonged time to conception.
Hernaez et al., 2021	Retrospective, Norway	28,341 women who are pregnant or have given birth to a child (MoBa cohort study).	BMI: WHO criteriaInfertility: “How many months of trying did it take to conceive?”TTP >12 months = Infertility.	Age, education level, smoking, number of previous births.	Infertility odds ratio (OR): obesity (OR = 1.03), overweight (OR = 1.10)Positive correlation between BMI and infertility for BMI values >22.1.	BMI and infertility exhibit an exponential relationship.
Zhu et al., 2022	Cross-sectional, USA	3623 women aged 18–45 from the NHANES 2013–2018 study, with provided information on BMI, fertility, and other additional abnormalities.	BMI: WHO criteriaInfertility:“Have you ever tried to get pregnant for at least 1 year and failed?” Answer “yes” = infertile, “no” = fertile.	Age, ethnicity, education, marital status, income-to-poverty ratio, alcohol consumption, active smoking, diabetes, hypertension, previous pregnancy, physical exercise, sedentary time.	Infertility odds ratio (OR): obesity (OR = 1.74), overweight (OR = 0.85)Nonlinear relationship, with a 3% increase for each unit rise in BMI for women with BMI ≥19.5 kg/m^2.U-shaped curve: very high and very low BMI values increase the infertility odds ratio (OR).	Obesity affects female fertility. There is a need to maintain a healthy BMI before conception.
Tang et al., 2023	Cross-sectional, USA	3542 women 20–45 years old from NHANES 2013–2020, with sufficient information regarding fertility and infertility. Excluded if they had undergone hysterectomy or bilateral oophorectomy, incomplete information on BMI/WC and metabolic disorders, or BMI <18.5 kg/m^2.	BMI + WC: WHO criteriaInfertility:“Have you ever tried to get pregnant for at least 1 year and failed?” Answer “yes” = infertile, “no” = fertile.	Age, ethnicity, marital status, education level, income-to-poverty ratio, alcohol and smoking status, previous pregnancy, physical activity.	Infertility odds ratio for WC (OR): obese (OR = 2.18), overweight (OR = 1.46). A 2% increase for each cm increaseInfertility odds ratio for BMI (OR): obese (OR = 1.83), overweight (OR = 0.92).	Obesity increases the risk of infertility in women in the United States.
Yin et al., 2023	Cross-sectional, USA	1509 women aged 18–45 from NHANES 2017–2020.	WC: sample divided into tertilesInfertility: “Have you ever tried to get pregnant for at least 1 year and failed?” Answer “yes” = infertile, “no” = fertile	Age, income-to-poverty ratio, minutes of sedentary activity, meals from pizzerias or fast food restaurants, total cholesterol, HDL, race, marital status, education level, diabetes, hypertension, LDL levels.	Association between WC and infertility (OR): an increase of 1 cm in WC increases the risk of infertility by 2%. 3rd trimester (OR = 1.21)Nonlinear relationship between WC + infertility: for WC <116.6 cm, the risk of infertility increases by 3% for each 1 cm increase.	Management of WC in women as a preventive measure for infertility.
Ke, Feng and Chen, 2023	Cross-sectional, USA	3239 women aged 18–45 from NHANES 2013–2018	WC: divided into quintilesInfertility: “Have you ever tried to get pregnant for at least 1 year and failed?” Answer “yes” = infertile, “no” = fertile.	Age, ethnicity, education level, marital status, income-to-poverty ratio, recreational activities, smoking up to 100 cigarettes in life, alcohol consumption, hypertension, diabetes, BMI, reproductive factor (pregnancy).	Infertility odds ratio(OR) + WC: quintile 5 (OR = 2.64)An increase of 1 cm in WC is associated with a 3% increase in the risk of infertility.A nonlinear relationship between WC and infertility, but dose dependent.	The relationship between waist circumference and infertility is positive and dose-dependent, regardless of BMI value, for women in the United States.
Boxem et al., 2024	Prospective, Netherlands	3604 women over 18 who participated in the Generation R Next study, either wishing to conceive or pregnant.	BMI: before or during the early stages of pregnancy (WHO criteria)TTP:1. Pregnant = Date of the start of conception attempts to the first day of the last period.2. Non-pregnant = Date of the start of conception attempts to the date of the last tracking/counting/end of the study.TTP >12 months = Infertility.	Age, ethnicity, education level, smoking, alcohol consumption, previous pregnancies, previous miscarriages.	Infertility odds ratio (OR):obese (OR = 1.67),overweight (OR = 1.35)For each unit increase in BMI, the OR increases by 2%.Low fecundability ratio (FR) in women with high BMI:obese (FR = 0.72),overweight (FR = 0.88)For each unit increase in BMI, the chances of fertility decrease by 2%.	Maintaining normal BMI limits before and during pregnancy is an important factor in reducing the chances of infertility.
Wang et al., 2024	Cross-sectional, USA	1577 women aged 18–44 from the NHANES 2017–2020 study. Excluded if they had undergone hysterectomy or bilateral oophorectomy, were pregnant, had incomplete information on WC, height and weight, or sleep status/sleep problems.	BMI + WC: (WHO criteria)Infertility: “Have you tried to get pregnant for at least 1 year without success?” and “Have you ever visited a doctor or healthcare provider because you were unable to conceive?” Answer “yes” = infertile, “no” = fertile	Age, marital status, smoking status, number of live births, hypertension, diabetes	Infertility odds ratio (OR):BMI: overweight/obese (OR = 1.17)WC: obesity (OR = 1.25)	No significant correlation was found between weight and infertility.
Zhang et al., 2024	Prospective, China	1684 women aged 20–49 years (NFPCP), with partners aged ≥20 years, not pregnant at the start of the study, who report wanting a child and are trying to conceive without contraception.	BMI: (WGOC criteria)TTP:1. Pregnant = (Date of last menstrual cycle before pregnancy − Date of last menstrual cycle at tracking)/30 + 12. Non-pregnant = (Date of last cycle at tracking − Date of last cycle at examination)/30	Age, profession, exposure to smoking, menstrual cycle regularity, sleep quality, frequent consumption of fast food, exercise frequency, frequency of taking dietary supplements.	Fecundability ratio (FR): overweight/obese (FR = 0.78).	Maintaining a normal BMI before conception is important to avoid prolonged time to conception.

Abbreviations: BMI: body mass index, WHR: waist-to-hip ratio, WC: waist circumference, WHO: World Health Organization, WGOC: Working Group of Obesity China, TTP: time to pregnancy.

Results from cohort studies

In their prospective study McKinnon et al.²¹ found that for women with BMI categories of 40–44 kg/m² and ≥45 kg/m², fertility ratios (FR) were significantly reduced by more than 39% compared to those in the normal BMI range (18–24 kg/m²). Similar trends were observed for WC and WHR, though not statistically significant. The study of Loy et al.²² found that women with BMI between 23 and 27.4 kg/m² and BMI >27.5 kg/m² had a statistically significant reduction in fertility by 34% and 47%, respectively, compared to women with a normal BMI. The study by Mena et al.²⁴ found that obese women had a 36% significantly higher risk of infertility (95% CI: 1.14–1.63). Furthermore, the incidence ratio (IR) was statistically high in women with normal/underweight BMI (95% CI: 2.53–3.08), followed by overweight (95% CI: 3.02–3.93) and obese women (95% CI: 3.54–4.71), confirming a positive association between higher BMI and fertility problems. A retrospective study by Zhang et al.²⁵ showed that overweight and obese women had, respectively a 5% and 20% significantly reduced chance of fertility, in the adjusted model (p < 0.05). A non-linear relationship was noted, with the best BMI values for shorter TTP being within the normal BMI range. The retrospective study conducted by Fang et al.²³ found a significantly increased risk of prolonged TTP among overweight and obese women (p < 0.05). The risk of infertility was also 8% higher for the same group of women. The correlation between BMI and reduced fertility was significant for BMI >22 kg/m² (reference BMI = 22 kg/m²). Moreover, the study by Hernáez et al.²⁶ found a 10% higher incidence of infertility in overweight women compared to women of normal weight (p < 0.001). Additionally, a positive, non-linear relationship was found between BMI and infertility after the BMI threshold of 22.1 kg/m². Boxem et al.²⁷ found that every increased unit in BMI was associated with a 4% increased likelihood of infertility, with 35% and 67% increased risks for overweight and obese women, respectively, compared to women with normal BMI (p < 0.05). The study also found that TTP was extended in overweight and obese women by 18% and 22%, respectively (p < 0.05). Also, the study by Zhang et al.²⁸ found that women in the overweight/obese categories had 22% reduced fertility compared to women with normal BMI (p < 0.05) (see Table 4).

Discussion

This systematic review aimed to examine the relationship between obesity and infertility in a total sample of 2,409,497 women demonstrating that obesity is associated with an increased risk of infertility. In particular, our findings indicate that centrally obese women have up to 2.6 times higher infertility risk compared to women without central obesity. Moreover, women with increased BMI values experienced both a prolonged TTP (20%–58%) and a higher infertility risk (3%–67%) compared to women with lower BMI. Moreover, in most of the studies, overweight women had slightly higher fecundability ratios (5%–36%) and lower infertility risk (10%–35%) compared to obese women. Additionally, BMI and WC indexes appear to be more consistent in their results compared to WHR, while the relationship between WHR and fertility was more conflicting. However, only two studies investigated the relationship of WHR and infertility and probably more research is needed for more concrete results.

Previous studies tried to examine the association between obesity and fertility using other measures-outcomes while demonstrating similar findings. Particularly, a recent systematic review by Turner et al.²⁹ examined studies investigating the relationship between BMI and pregnancy achievement, primarily through assisted reproductive technology. The results showed that with higher BMI more time was required for ovarian stimulation compared to women with a normal BMI. Moreover, the findings of a recent systematic review and meta-analysis indicate that obese, overweight, and the combined categorization of overweight/obese women experience reduced fertility due to prolonged TTP, with corresponding fertility odds ratios (FOR) for each category as follows: FOR = 0.76 (obese), FOR = 0.93 (overweight), and FOR = 0.85 (overweight/obese).⁸ In contrast, a retrospective study observed that 3 study groups of BMI (BMI <19 kg/m², BMI >30 kg/m², BMI 19–30 kg/m²) had comparable results in the case of live birth rates 27.3%, 31.9% and 22.2%, respectively.³⁰

Another study found that BMI and WC are positively correlated, and women with BMI ≥25 kg/m² and a WC ≥77 cm had significantly lower birth rates (OR = 1.38) than women with BMI between 18.5 and 25 kg/m² and a WC <77 cm (OR = 1.54).³¹ These findings are indicators that both BMI and WC are indexes with potential impact on fertility outcomes, either if they are analysed together or separately. On the other hand, results regarding the relationship between WHR and fertility are more conflicting. While the studies included in the current review showed no significant findings, a previous study that examined the association between infertility and WHR using data from the NHANES 2017–2020 survey concluded that for every 0.1 cm increase in WHR, the risk of infertility increased by 35% (OR = 1.35), while for WHR ≥0.85, this risk increased by 75% compared to women with WHR ≤0.85 (OR = 1.75).³²

The mechanisms in which obesity is related to fertility are still under investigation. It seems that excess adipose tissue with BMI above 27, can affect the reproductive hormone balance by interrupting the HPO axis.³³ More specifically, obesity leads to elevated insulin levels, which enables the higher production of ovarian androgens. These androgens are then aromatised to oestrogens, causing a negative feedback loop in HPO axis, resulting in ovulation issues due to gonadotropin imbalances.³⁴ Moreover, other mechanisms suggest that obesity directly affects the oocyte and the preimplantation embryo by disruption of meiotic spindle formation and mitochondrial function.³⁵ Additionally, the literature suggests that central obesity regardless of BMI values, is associated with higher testosterone levels and lower sex-hormone-binding-globulin (SHBG) concentrations, which ensures that fat distribution significantly impacts hormone concentrations and eventually, adverse fertility outcomes.³⁶

In this systematic review BMI and WC appeared as more sensitive indexes than WHR about their influence on infertility risk. However, the cross-sectional study by Wei et al.³⁷ found, in a sample of 726 women, that obese women had twice the risk of experiencing menstrual cycle irregularities compared to women of normal weight, regardless of whether BMI (OR = 2.61), WC (OR = 2.28), or WHR (OR = 2.27) was measured. Moreover, a study that compared the relationship between BMI, WC and WWI (weight-adjusted-waist-index), concluded that the third index had stronger connection with the risk of infertility.³⁸ The above findings may indicate the different relationships these indexes have on each outcome of the woman's reproductive system, as some of them appear to be more sensitive in specific outcomes than others. This is a valuable finding that may introduce a new path in focusing on the target index for specific reproductive problems in future research.

Notably, other metabolic-endocrine disturbances such as insulin resistance and polycystic ovary syndrome (PCOS) may significantly impair ovulatory function and fertility. In particular, PCOS is one of the most common endocrine disorders among women of reproductive age and is closely associated with insulin resistance and obesity.³⁹ Although none of the included studies investigated PCOS or insulin resistance, these factors are highly relevant to the relationship between obesity and infertility.^39,40 Given that many of the women in the included studies were overweight or obese and that BMI was a key exposure variable, it could be assumed that some of the infertility observed may be mediated through undiagnosed PCOS or insulin resistance. Future studies should aim to explicitly include these endocrine conditions to better elucidate the mechanisms linking obesity with impaired fertility.

To the best of our knowledge, the strength of this review lies in being the first to examine the relationship between obesity and infertility using a variety of indices (three for obesity and two for infertility). Moreover, the indices used to identify infertility include both numerical and non-numerical measures, ensuring more reliable findings. On the other hand, this study has some limitations. Firstly, both exposure and outcome data were self-reported by the participants. This practice may introduce information bias. Furthermore, studies conducted retrospectively increased the risk of recall bias. It is also worth mentioning that delayed pregnancy and sterility may also be influenced by male infertility, which could have somewhat affected the results of this systematic review.

Overall, both central and general obesity may negatively impact reproductive function in women, leading to reduced fertility. Our findings suggest a potential causal relationship between obesity and infertility, emphasizing the need for further research to better understand the underlying mechanisms through which obesity contributes to reproductive dysfunction. It is also crucial to investigate how these mechanisms are associated with specific obesity indexes, as this could help identify more precise risk factors. Additionally, future studies should consider the role of hormonal and metabolic imbalances linked to obesity. Understanding these factors may guide the development of targeted interventions and improve fertility outcomes in women affected by obesity. Such insights could also inform clinical guidelines and public health strategies for reproductive health management.

Conclusions

Overweight and obese women (BMI) were associated with significantly higher infertility risk and TTP prolongation despite the population criteria. The same pattern was observed for centrally obese women and a significant, over doubled TTP prolongation risk. Generally, BMI and WC had non-linear relationships with infertility risk or TTP, but exponential growth of negative outcomes was associated with general or central weight gain. WHR and infertility indices presented variable relationships, depending on the population. Overall, this study summarises the need for maintaining a healthy weight for reducing negative fertility outcomes, as well as inspiring the scientific community to focus on biological mechanisms of female reproductive system that are affected by each obesity category.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interests

The authors declare that they have no conflict of interests.