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Obesity and reproduction: a committee opinion (2021)


Over the past four decades, obesity (body mass index [BMI] > 30 kg/m2 in Western nations) has become a global epidemic affecting an estimated 603.7 million adults, representing 12% of the world’s adult population (1). In 1980, 19% of adult American women and 13% of adult American men were obese (2). By 2017–2018, 42% of American women and 43% of American men were obese. Severe obesity (BMI > 40 kg/m2) now affects 11.5% of adult American women. Ethnic disparities in obesity prevalence exist. Fifty-seven percent of non-Hispanic black, 44% of Hispanic, 40% of non-Hispanic white, and 17% of non-Hispanic Asian American women are obese (3). Fifty-one percent of pregnant American women are overweight or obese at the time of conception (4). 
 
The Global Burden of Disease 2015 Obesity Collaborators estimate that high BMI results in 4,000,000 deaths worldwide annually, or 7.1% of all-cause mortality (1, 5). In the United States, the estimated annual medical cost of illness related to obesity approaches $150 billion, excluding the cost of maternal morbidity and adverse perinatal outcomes (6). 
 
Obesity has adverse effects on reproduction, including on ovulatory and menstrual function, natural fertility and fecundity rates, infertility treatment success rates, infertility treatment safety, and obstetric outcomes. The ability to deliver optimal care to women with obesity can be limited by difficulties in transvaginal ultrasound imaging of the ovaries and safety considerations, such as difficulty in maintaining an airway during oocyte retrieval. Reproductive care specialists are, thus, confronted with the challenge of treating infertility in the increasingly common setting of obesity. Furthermore, previous assumptions that weight loss interventions improve reproductive outcomes are being challenged by the findings of several recent published studies (7–9). 

This document outlines the adverse effects of obesity on human reproduction. An assessment of the  therapeutic benefits of lifestyle modification, medical management, and bariatric surgery is offered. The issues of safety and BMI treatment thresholds are addressed.  

DEFINITION OF OBESITY 

Obesity is a disease of excess body fat, and it increases the risk of a number of common conditions, including type 2 diabetes, dyslipidemia, hypertension, coronary heart disease, cholelithiasis, endometrial and postmenopausal breast cancer, stroke, osteoarthritis, and infertility (10–17). 
 
Body fat is difficult to measure directly and is often estimated by the BMI calculation, a formula first described in the 19th century and calculated as body weight in kilograms divided by height in meters squared (18). A number of expert committees have established BMI classifications that aid in screening for individuals at risk of disease related to excess body fat and identifying individuals who may benefit from weight loss interventions. The World Health Organization classification system is commonly used in Western nations and is outlined in Table 1 (19).

Table 1


WHO classification of obesity

Classification BMI (kg/m2) Risk of comorbidities
Underweight <18.5 Low (but risk of other clinical problems increased)
Normal range 18.5-24.9 Average
Overweight >25  
     Pre-obese 25-29.9 Increased
Obese >30  
     Obese class 1 30-34.9 Moderate
     Obese class 2 35-39.9 Severe
     Obese class 3  >40 Very severe
Adapted from: Obesity: preventing and managing the global epidemic.  Report of a WHO Consultation (WHO Technical Report Series 894), 2000 (19)
A BMI of 30 kg/m2 is often used to define obesity at a population level because it represents a reasonable cutoff in balancing the sensitivity and specificity for identifying people at risk of disease related to excess body fat (20). Of note, different BMI cutoffs have been recommended for specific populations on the basis of the local prevalence of adiposity-related disease and population-specific associations between BMI, percentage of body fat, and health risks (21). 
 
Body mass index cutoffs are easily accessible as clinical screening tools, but they do not account for individual differences in frame size and lean body mass. Additionally, they do not help in determining disease risk related to body fat for individuals who are classified as normal BMI, nor do they differentiate by fat distribution pattern (i.e., ‘‘apple’’ vs. ‘‘pear’’ fat distribution), with central obesity associated with greater metabolic risk. Adult weight gain is a readily interpretable number that is more specific to individuals, and it addresses risk tied to excess body fat in individuals with a normal BMI (10–12, 14, 20). This number may be particularly significant for reproductive-aged individuals because most body fat accrues after the age of 19 years in women and after the age of 20 years in men. Adult weight gain is an important risk factor for chronic disease and reduced fecundity (22). Obesity can impair reproduction in both women and men, leading to infertility in couples trying to conceive and subsequent complications in pregnancy (23–25).  

OVULATION AND MENSTRUAL CYCLE ABNORMALITIES 

Women with increased weight, amenorrhea, and hyperandrogenism were described by the French surgeon/obstetrician Par'e as early as 1633 (26). Stein and Leventhal (27) reported obesity in three of the seven amenorrheic–oligomenorrheic patients in their seminal description of the Stein–Leventhal syndrome. Possibly the first systematic study to investigate the relationship between obesity and menstrual disturbances documented a 48% prevalence of obesity in 60 amenorrheic women compared with a 13% prevalence in a eumenorrheic control group (28). Most studies report a prevalence of menstrual cycle irregularities in women with obesity of 30%–36% (29–32); however, ranges of less than 10% (33) to greater than 50% (34, 35) have been reported. In a case-control study of 597 women with anovulatory primary infertility compared with 1,695 primiparous controls, the crude and adjusted (for age and exercise) relative risks of primary anovulatory infertility were 3.1 (95% confidence interval [CI], 2.2–4.4) and 2.4 (95% CI, 1.7–3.3) above a BMI of 27 kg/m2 (25). The prevalence of amenorrhea or oligomenorrhea increases with increasing degrees of overweight or obesity in adulthood (32, 33) and in adolescence (31). Childhood obesity at the age of 7 years is an independent predictor of menstrual problems by the age of 33 years (36). 
 
Ovulatory dysfunction is more common in women with obesity (27, 28, 37). Much of this ovulatory dysfunction is likely confounded by a diagnosis of polycystic ovary syndrome (PCOS). Data from the Nurses’ Health Study illustrate that as BMI rises, the risk anovulatory infertility increases (17). In addition, a greater BMI at the age of 18 years predicted anovulatory infertility, with and without the diagnosis of PCOS (relative risk [RR], 1.0, and BMI, 20.0–21.9; 1.3 and BMI, 24–25.9; 1.7 and BMI, 26–27.9; 2.4 and BMI, 28–29.9; 2.7 and BMI, 30–31.9; and 2.7 and BMI, >32 kg/m2). Body fat distribution is also important because anovulatory women have a greater waist circumference and more abdominal fat than ovulatory women of similar BMI (38). Another study supported this conclusion by demonstrating that abdominal body fat was more predictive of ovulatory dysfunction than total body fat (39). 
 
Obesity is a common symptom of PCOS, and thus, PCOS is a confounding feature of these associations. Prevalence data delineating the contribution of BMI on the risk of ovulatory dysfunction when the diagnosis of PCOS has been excluded lacks clarity, in part because of the varied diagnostic criteria and phenotypes for PCOS. Whereas the degree of obesity among women with PCOS has increased over time, reflecting the rise observed in the general population (40), it is significant to note that the risk of PCOS is only minimally increased with obesity (40, 41). 
 
Improved ovulation rates and menstrual regularity have been demonstrated with modest weight loss through lifestyle modification with and without adjunctive weight loss medications in women with PCOS (9, 42–46). Correction of amenorrhea occurs in several women with obesity after bariatric surgery (30). It should be noted, however, that determining the true prevalence or risk of menstrual cycle irregularities in obese women is challenging. A limitation is that most studies of menstrual irregularity rely on retrospective reporting by the study subjects and the validity of retrospective self-reported menstrual cycle length has been challenged, particularly in women with short or long mean menstrual cycle lengths (47). 
 
Reproductive hormone differences exist in women by BMI category, even among those with regular menstrual cycles in each group, suggesting that menstrual cycle dysfunction in obesity falls along a spectrum. Ovulatory menstrual cycles in women with obesity are characterized by lower total cycle luteinizing hormone (LH), decreased early follicular phase LH pulse amplitude, lower total cycle follicle-stimulating hormone, longer follicular phases, shorter luteal phases, and decreased luteal phase progesterone metabolite compared with normal-weight ovulatory women (48, 49). 
 
Central obesity and visceral fat can result in insulin resistance and hyperinsulinemia. Insulin resistance promulgates hyperandrogenemia through direct actions on the ovary and through decreased hepatic sex hormone-binding globulin production, often suggestive of PCOS. Hyperandrogenemia, increased peripheral aromatization of androgens to estrogens in adipose tissue, storage of sex steroids in adipose tissue, altered levels of leptin and other adipokines, altered insulin-like growth factor binding protein production, and impaired granulosa cell function all contribute to menstrual irregularities through disruption of the hypothalamic–pituitary– gonadal axis (25, 30, 50–52).  

ALTERED OVARIAN RESPONSIVENESS AND OOCYTE QUALITY WITH FERTILITY TREATMENTS 

In addition to higher rates of ovulatory dysfunction, obesity has been associated with worse outcomes after infertility treatment. Data suggest that altered folliculogenesis and diminished oocyte quality are potential mediators. 

Responsiveness to Ovarian Stimulation 

In normogonadotropic anovulatory women, increased BMI and abdominal obesity are associated with decreased odds of ovulation in response to clomiphene citrate (increased BMI, odds ratio [OR], 0.92 [0.88–0.96]; increased waist-to-hip ratio, OR, 0.60 [0.40–0.89]) (53). Results from a large randomized trial showed that the live birth rates (LBRs) were greater after letrozole treatment than those after clomiphene citrate, primarily among women with elevated BMI, suggesting altered pathophysiology or underdosing of clomiphene citrate (54). In addition, women with obesity treated with gonadotropins for ovulation induction require higher doses of medication and produce fewer follicles at a given dose (55). Several large retrospective analyses (1,721 to 8,145 women undergoing assisted reproductive technologies [ARTs]) also confirm that obesity impairs ovarian responsiveness to gonadotropin stimulation (i.e., increased duration, amount of gonadotropin administered, increased cycle cancellation; fewer oocytes retrieved) (56–60). 

Oocyte Quality 

Several studies have investigated the association between obesity and oocyte and resultant embryo quality. Women with obesity undergoing in vitro fertilization (IVF) have an altered follicular environment with higher levels of insulin, markers of inflammation, and elevated levels of free fatty acids, which were correlated with abnormal cumulus-oocyte complexes (61–63). Oocytes from women who are overweight or obese are smaller (63, 64) than those from normal-weight controls. However, fertilization rates have been inconsistently linked to maternal BMI (56, 65–69). Whereas the blastulation rates and metabolics of developing embryos appear to be influenced by obesity (63, 70), the pportion of euploid embryos is not different among BMI categories (71). In 2016, two large retrospective studies using national data from the Centers for Disease Control and Prevention's National ART Surveillance System and from the SART Clinic Outcome Reporting System database analyzed the relationship between BMI and IVF outcomes. Both studies demonstrate a decrease in pregnancy rate and LBR with increasing BMI (72, 73). However, the age-related decline in fertility has a greater impact than BMI on LBR at older ages, suggesting that taking time to lose weight before IVF may be detrimental for older women with overweight or obesity (74) (Fig. 1). In addition, ovulation induction in women with PCOS results in lower LBRs in women as BMI increased (75). 
 
These human studies are supported by diet-induced obese mouse models. In these models, obesity impairs oocyte quality through mitochondrial dysfunction, increases reactive oxygen species, and is associated with abnormal meiotic spindles and chromosomal alignment (76, 77). Interestingly, mouse models have shown that interventions such as weight loss, increased physical activity, and antioxidant therapy are unable to reverse the oocyte quality provoked by the diet-induced obesity (78–80). 
 
In conclusion, increasing BMI is associated with lower ovarian responsiveness to ovulation induction as evidenced by the need for higher doses of oral agents and gonadotropins and the lower number of oocytes retrieved during IVF. In addition, oocyte quality is impaired in both obese animal models and human clinical studies. In a linear manner, higher BMI is correlated with lower implantation and clinical pregnancy rates and LBRs when undergoing IVF/intracytoplasmic sperm injection treatment. This effect is most prominent in younger reproductive-aged women and is significantly attenuated with advancing reproductive age (74).  

ENDOMETRIAL FUNCTION 

A number of studies have investigated IVF outcomes in obese donor oocyte recipients as a way to independently evaluate obesity’s clinical impact on endometrial receptivity and function. Some have demonstrated no effect, whereas others have shown a negative effect with lower implantation rates (72, 81, 82). Regardless, obesity is a well-known risk factor for endometrial hyperplasia and cancer (15). On a molecular level, the endometrium from women with obesity demonstrates increased steroid receptor staining and altered expression of other genes that is more pronounced in the presence of infertility (83, 84).  

MISCARRIAGE RATES 

Obesity has been associated with an increased risk of pregnancy loss (56, 58, 85–89) in most, but not all, studies (55, 57, 90). Differences in outcomes between studies are likely related to varying levels of comorbidities and the multifactorial mechanisms through which BMI can influence pregnancy outcomes. Both obesity and miscarriage have been associated with thyroid dysfunction (91, 92), insulin resistance (93, 94), leptin resistance (95–97), lipotoxicity and inflammation (25, 98–100), as well as sleep dysfunction (101–103) and mental health (104–106). 
 
In a 2011 meta-analysis evaluating the association of obesity and miscarriage in unassisted conceptions, women with obesity were 1.3 times more likely to have a pregnancy loss (OR, 1.31; 95% CI, 1.18–1.46) (107). This association was further confirmed in a prospective observational study of more than 18,000 nulliparous Chinese women with unassisted conceptions, in which obesity was associated with an increased risk of miscarriage (adjusted RR, 1.51; 95% CI, 1.13–2.02) (108). 
 
Similarly, women with obesity who conceived with ART also have higher rates of miscarriage. This association was demonstrated in analyses of SART and CDC data (72, 73). In addition, a large 2019 analysis of first frozen embryo transfers with good-quality embryos demonstrated an association between obesity and early pregnancy loss (adjusted OR, 1.46; 95% CI, 1.15–1.87) (65). Finally, a meta-analysis limited to only women with recurrent miscarriage also suggested that obesity is associated with higher miscarriage rates (OR, 1.75; 95% CI, 1.24–2.47) (109). 
 
The mechanism of action underlying the association between obesity and early pregnancy loss has been evaluated using donor oocyte models. A retrospective study of more than 9,000 women was performed, where oocyte donors were of normal weight and oocyte recipients were of varying BMI categories (110). The results demonstrated a decrease in live birth, but no difference in clinical miscarriage rate, with increasing BMI of the recipient. In contrast, a similar analysis of data from the SART database from 2008 to 2010 demonstrated an increase in miscarriage rate when the recipient BMI was >40 kg/m2 (adjusted OR, 1.67; 95% CI, 1.05–2.63) (111). 
 
Miscarriages in the general population have high rates of aneuploidy, which has well been documented to increase with age. However, an analysis from a well-characterized recurrent pregnancy loss database demonstrated that in pregnancy losses at <10 weeks’ gestational age, women with obesity with recurrent pregnancy loss have a 58% chance of having a euploid loss compared with 37% in women without obesity (RR, 1.63; 95% CI, 2.08–2.47) (112). Similarly, an unselected analysis of products of conception from one academic center indicated that women with obesity had a 46% euploid loss compared with 34% in nonobese individuals (OR, 1.56; 95% CI, 1.25–1.95) (113). Interestingly, when blastocyst embryos are biopsied, women with obesity have similar proportion of euploid embryos (71). The observed higher rate of euploid miscarriages in women with obesity suggests that higher BMI is an independent risk factor for miscarriage. 
 
In summary, various studies demonstrate a link between obesity and miscarriage risk regardless of mode of conception. However, the adjusted ORs range between 1.2 and 1.9, suggesting that while a link exists, the association is modest and may be influenced by confounding factors.
 

MATERNAL–FETAL ENVIRONMENT 

Maternal obesity is associated with increased obstetric and neonatal risk (23). In a cohort of 106,552 women in the United States, the relative risks for pregnancy complications attributable to obesity in women without documentation of other chronic diseases (i.e., metabolically healthy but obese) are outlined in Table 2 (114). While adverse outcomes associated with maternal obesity occur in the absence of other contributing risk factors, comorbidities such as preconception hypertension, obstructive sleep apnea, and diabetes are likely significant in the pathophysiology and incidence of these outcomes (23). Of additional concern for pregnant women with obesity is the limitation excess adiposity places on important assessment tools used during gestation, such as assessment of fetal growth via fundal height and anatomic survey of the fetus with ultrasound (23, 115). Such limitations may also contribute to the incidence of some adverse pregnancy outcomes for women with obesity. Women with obesity who achieve even small weight reductions before pregnancy may have improved pregnancy outcomes (23).

Figure 1


Obesity-Fig1.png

OBESITY AND MALE REPRODUCTION 

As the prevalence of obesity has increased steadily over more than three decades, a concurrent decline in semen quality has been described (116, 117). The mechanisms by which obesity may result in diminished semen quality and male factor infertility include endocrine alterations, sexual dysfunction, and other medical issues including diabetes mellitus (118), sleep apnea (119), or scrotal hyperthermia due to body habitus (120–122). 
 
Obesity in men is associated with an increased incidence of oligozoospermia and asthenozoospermia in some (123–131), but not all (132–138), studies. One purported and generally accepted mechanism for lower sperm counts is related to aromatization of testosterone to estradiol in peripheral adipose tissue with resultant estradiol-mediated negative feedback and suppression of the hypothalamus–pituitary–testis axis (139, 140). Moreover, increased abdominal adiposity in men of subfertile couples has been associated with reduced sperm count, concentration, and motility (129). Male obesity may also alter sperm function (141), increase sperm DNA damage (132, 142–146), decrease sperm mitochondrial activity (144, 145), and induce seminal oxidative stress (147). Emerging data suggest that sperm epigenetics is altered in men with obesity (148), with potential implications for future offspring. With respect to ART, male obesity appears to impact blastocyst development (124), with conflicting reports related to clinical pregnancy, miscarriage, and LBRs (111, 124, 126, 132, 141, 149–152). A systematic review found that obese men were more likely to experience infertility (OR, 1.66; 95% CI, 1.53–1.79), their rate of live birth per cycle of ART was reduced (OR, 0.65; 95% CI, 0.44–0.97), and they had a 10% absolute risk increase of pregnancy nonviability (153). A second systematic review and meta-analysis was consistent with this study, finding men with obesity having a decreased LBR after IVF (OR, 0.88; 95% CI, 0.82–0.95) (154). 
 
An inverse relationship between BMI and testosterone is well established (142, 155). Suppression of sex hormone-binding globulin by insulin in men with obesity increases androgen availability for estrogen aromatization, which may lead to reduced gonadotropin secretion (122, 137, 141, 156, 157). Simultaneously, men with obesity have decreased total and bioavailable testosterone levels (134, 137, 139, 141, 147, 157–159) as well as reduced inhibin B concentrations (137, 156, 157, 160), combined with diminished LH pulse amplitude (142). This hormonal profile suggests enhanced estrogen negative-feedback inhibition from increased adipose-derived aromatase activity (161), along with decreased formation of inactive 2-hydroxyestrogens (122, 141, 147, 139, 162–165). Consequently, obesity in men is accompanied by decreased Leydig cell testosterone secretion, with testosterone levels negatively correlated with fasting insulin and leptin levels (159, 164, 166). 
 
In men with obesity, the scrotum remains in closer contact with surrounding tissue than in normal-weight men, predisposing to increased scrotal temperature that may adversely affect semen parameters (141, 167, 168). However, proposed treatments aimed at lowering scrotal temperature (‘‘scrotal hypothermia’’) or reducing the amount of scrotal fat are impractical and unproven (169). 
 
A diagnosis of male infertility may provide a unique opportunity to motivate men with obesity to lose weight. Weight loss results in increased testosterone levels (170, 171) and improvements in sexual function (172, 173). A prospective study assessing shorter- and longer-term impacts of diet-induced weight loss in 118 over-weight (N ¼ 32) and obese (N ¼ 86) men tracked testosterone and self-reported sexual function, as reported by the International Index of Erectile Function (IIEF), during a 12-week weight loss period, followed by 40 weeks of maintenance (171). The total testosterone level increased, and the IIEF improved during the acute weight loss period; the total testosterone level continued to increase, and the free testosterone level increased during the maintenance period, whereas the IIEF remained stable. 
 
However, the interplay between weight loss and spermatogenesis is less definitive. There is a dearth of data regarding changes in semen parameters after weight loss in obese men. One study followed 43 men with short-term follow-up at 14 weeks after weight loss achieved via diet and exercise. Men with the largest degree of weight loss demonstrated the most significant increases in sperm count and normal morphology (157). The few published studies exploring bariatric surgery-mediated weight loss and semen parameters provide conflicting results and suffer from small sample sizes and relatively short follow-up intervals (174–177).  

MANAGEMENT 

Medical Treatment 

Weight loss medications may be beneficial when used in conjunction with lifestyle interventions and may increase the likelihood that patients adhere to behavioral and lifestyle interventions, perhaps because of the positive feedback of the rapidity and degree of weight loss. Most result in weight loss through temporary effects on appetite, and thus, patients must reduce energy intake and/or increase energy expenditure in the long term to sustain weight loss achieved with medications. The use of weight loss medications may be considered in patients with a history of unsuccessful weight loss who meet label indications (178) but should be tailored to the knowledge, experience, and comfort level of the prescribing physician. Alternatively, referral to a weight management provider with more experience in prescribing these medications may also be appropriate. 
 
Medications for treatment of obesity, except for orlistat, typically target appetite to effect weight loss. They work primarily by promoting satiety through stimulation of pro-opiomelanocortin neurons in the arcuate nucleus, often mediated via serotoninergic, dopaminergic, or norepinephrine-releasing agents/reuptake inhibitors (178). Orlistat blocks absorption of fat calories and reabsorption of glucose (178). Some medications are associated with elevation in blood pressure and pulse rate, whereas others may increase the risk of serotonin syndrome in patients using a selective serotonin reuptake inhibitor or serotonin– norepinephrine reuptake inhibitor. Thus, caution is advised in prescribing these medications to patients with cardiovascular disease, hypertension, history of cardiac arrhythmias, seizures, depression, and anxiety and patients using pharmacotherapy for smoking cessation. 
 
Phentermine is approved by the US Food and Drug Administration (FDA) for short-term use and is currently one of the most commonly prescribed weight loss medications, likely because of its low cost. It has been shown to induce over 7% weight loss at 6 months (179). Current recommendations indicate that the dose should only be increased if the patient is not achieving clinically significant weight loss and should be followed every month while undergoing dose escalation, which may extend to at least every 3 months when on a stable dose (178). Current data suggest that the potential for addiction is low (180); however, weight gain is likely to occur on discontinuation of the medication. The combination of phentermine plus topiramate has been approved for chronic management of obesity and has demonstrated a greater weight loss than with either agent alone. It is among the most efficacious of FDA-approved weight loss medications, with an average expected weight loss of 5%– 11% over 1 year (181, 182). 
 
In addition to phentermine/topiramate, orlistat, naltrexone/bupropion, and liraglutide are all FDA-approved for the chronic management of obesity. The average expected weight loss with these medications is 2.9–5.8 kg, making them less efficacious in comparison to the phentermine/topiramate combination. It is worth noting that very few of these medications have been studied in the context of infertility, and all are currently considered pregnancy category X (i.e., indicating that studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk on the basis of adverse reaction data from investigational or marketing experience, and the risks involved in the use of the drug in pregnant women clearly outweigh potential benefits) when used for the purposes of weight loss. Table 3 shows information regarding indications, side effects, and contraindications for commonly used weight loss medications.

Table 2


Obstetric complications of singleton pregnancies among women without prepregnancy diseases by prepregnancy obesity, Consortium on Safe Labor 2002–2008

Outcome Normal BMI     Overweight     Obese class 1     Obese class 2   ` Obese class 3    
  # (%) RR AR% # (%) RR AR% # (5) RR AR% # (%) RR AR% # (%) RR AR%
Gestational hypertensive disorders 3,351 (5)



-- -- 2096 (8) 1.65 (1.57-1.74) 3

1274 (11) 2.34 (2.20-2.49)

6 631 (13.2)



2.78 (2.56-3.01)

8.2 536 (17.3)

3.55 (3.26-3.86)

12.3
Gestational diabetes mellitus 1,834 (2.8) -- -- 1495 (5.7) 1.99 (1.86-2.13) 2.9 959 (8.3) 2.94 (2.73-3.18) 5.5 517 (10.8) 3.97 (3.61-4.36) 8 452 (14.6) 5.47 (4.96-6.04) 11.8
Cesarean delivery 14,872 (22.4) -- -- 7562 (28.7) 1.26 (1.23-1.29) 6.3 3936 (33.9) 1.49 (1.45-1.53) 11.5 1830 (38.3) 1.7 (1.64-1.77) 15.9 1457 (46.9) 2.01 (1.93-2.10) 23.6
Stillbirth 206 (0.3) -- -- 91 (0.4) 1.07 (0.83-1.37) 0.1 53 (0.5) 1.43 (1.05-1.96 0.2 15 (0.3) 1.01 (0.59-1.74) 0 14 (0.5) 1.41 (0.82-2.45) 4.7
Large for gestational age 5272 (7.9) -- -- 3171 (12) 1.52 (1.45-1.58) 4.1 1584 (13.7) 1.74 (1.65-1.83) 5.8 712 (14.9) 1.93 (1.79-2.07) 9 538 (17.3) 2.32 (2.14-2.52) 9.4
Congenital anomaly 3923 (5.9) -- -- 1673 (6.4) 1.08 (1.02-1.14) 0.5 728 (6.8) 1.07 (0.99-1.16) 0.9 317 (6.6) 1.12 (1.00-1.25) 0.7 449 (14.5) 1.2 (1.05-1.36) 1.4
NICU admission 5880 (8/9) -- -- 2848 (10.8) 1.16 (1.11-1.21) 1.9
1335 (11.5)
1.20 (1.13-1.27) 2.6 610 (12.8) 1.3 (1.20-1.41) 3.9   1.38 (1.26-1.51) 5.6


NICU, neonatal intensive care unit
RR adjusted for maternal age, maternal race, insurance type, marital status, parity, smoking and alcohol use
AR%:  attributable risk percent = percent of women with complication in the obesity class category minus the percent of women with the complication in the normal weight category.
Adapted from:  Kim, et al.  Obstetric and neonatal risks among obese women without chronic disease.  Obstetrics and Gynecology, 2016. PMID:  27275800 (114)
Metformin, although frequently used in patients with PCOS, is not considered a weight loss medication. It is a biguanide that increases peripheral sensitivity to insulin and inhibits hepatic glucose production, resulting in decreased circulating insulin levels. It may promote weight loss when used in combination with lifestyle interventions, although studies suggest that weight loss experienced with metformin is minimal (1.1 kg) (183, 184).  

Surgical Treatment 

Bariatric surgery is currently the most effective intervention for significant and sustained weight loss regardless of the type of procedure used (185–187). Patients may lose as much as 70% of excess weight within 12 months after surgery, and on average, 5 years after surgery, patients maintain approximately 50% of their excess weight loss (188, 189). These procedures cause weight loss by restricting the amount of food that the stomach can hold, by causing malabsorption of food, or by a combination of restriction and malabsorption. According to the American Society for Metabolic and Bariatric Surgery (ASMBS), the most commonly performed bariatric procedures are Roux-en-Y gastric bypass, sleeve gastrectomy, adjustable gastric band, and biliopancreatic diversion with duodenal switch, with the Roux-en-Y gastric bypass considered the gold standard of weight loss surgery (Fig. 2) (190). This procedure creates a small stomach pouch and attaches it to the jejunum to shorten the length of the intestinal tract. This leads to the restriction of the amount of food the stomach can hold as well as decreased absorption of calories by the small intestine. This often results in significant long-term weight loss; however, it is a more complex procedure, possibly resulting in higher complications rates, and can lead to long-term vitamin and mineral deficiencies requiring lifelong supplementation, particularly vitamin B12, iron, calcium, and folate. 
 
The laparoscopic sleeve gastrectomy is performed by removing approximately 80% of the stomach and works via restricting the volume the stomach can hold, helping reduce the amount of food consumed, and altering gut hormones that affect hunger, satiety, and blood glucose control (191). Rapid and significant weight loss results are comparable to the Roux-en-Y gastric bypass, with a similar risk of longterm vitamin deficiencies. The benefits over Roux-en-Y are that it does not require intestinal anastomosis and typically involves a shorter hospital stay. 
 
The adjustable gastric band procedure involves placement of an inflatable band around the upper portion of the stomach, creating a small stomach pouch above the band leading to weight loss because of food restriction rather than malabsorption. Because there is no malabsorption, there is very low risk of vitamin and mineral deficiencies. 
 
The biliopancreatic diversion with duodenal switch gastric bypass involves creating a tubular stomach pouch by removing part of the stomach and then bypassing a larger portion of the small bowel compared with the Roux-en-Y bypass. This procedure also causes favorable changes in gut hormones to reduce appetite and improve satiety; however, it also has a higher complication rate and risk of mortality compared with the other procedures. Additionally, it requires a longer hospital stay and has greater potential to cause protein, vitamin, and mineral deficiencies.

Table 3


Table of weight loss medications (178, 181)

Drug name FDA approval DEA schedule Avg weight loss Mechanism of action Side effects/Warnings Considerations /contraindications
 Sympathomimetics Shotr term use (<3 months)   3.6 kg Release of catecholamines such as dopamine and norepinephrine to suppress appetite
 
 
 
 
Headache, elevated blood pressure, elevated pulse, insomnia, dry mouth, constipation, anxiety, restlessness, tremor Pregnancy, breastfeeding, anxiety disorders, history of heart disease, uncontrolled hypertension, MAO inhibitors, pregnancy, breastfeeding, hyperthyroidism, glaucoma, history of drug abuse, sympathomimetic amines
     -   Phentermine   IV
     -   Diethylpropion   IV
     -   Benzphetamine   III
     -   Phendimetrazine   III
Orlistat Chronic use None 2.6 kg Lipase inhibitor Decreased absorption of fat-soluble vitamins, steatorrhea, oily spotting, flatulence with discharge, fecal urgency, oily evacuation, increased defecation, fecal incontinence Cyclosporines, chronic malabsorption syndrome, pregnancy, breastfeeding, cholestasis, levothyroxine, warfarin, antiepileptic drugs
Naltrexone SR/bupropion SR Chronic use None 5.0 kg Opioid receptor antagonist, dopamine and norepinephrine reuptake inhibitor Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, diarrhea, increase in blood pressure and heart rate, hepatotoxicity, angle-closure glaucoma Pregnancy and breastfeeding, uncontrolled hypertension, seizure disorders, anorexia nervosa, bulimia, drug or alcohol withdrawal, MAO inhibitors, chronic opioid use
Liraglutide Chronic use None 5.3 kg GLP-1 receptor agonist Nausea, vomiting, pancreatitis Pregnancy, breastfeeding, personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2
Phentermine /topiramate ER Chronic use IV 8.8 kg GABA receptor modulator, norepinephrine-releasing agent Increased heart rate, insomnia, dry mouth, constipation, paresthesia, dizziness, dysgeusia, suicidal behavior and ideation, acute myopia and secondary angle closure glaucoma, disturbances in attention or memory, metabolic acidosis, elevated creatinine Pregnancy, breastfeeding, hyperthyroidism, glaucoma, MAO inhibitors, sympathomimetic amines. Fetal toxicity has been reported and is recommended to obtain a negative pregnancy test before, and each month thereafter along with use of effective contraception.
A statement issued by the ASMBS in 2017, endorsed by the American College of Obstetricians and Gynecologists and the Obesity Society, noted that ‘‘bariatric surgery is effective in achieving significant and sustained weight loss in women with morbid obesity and has been shown in case-control studies to improve fertility. however, the specific impact of bariatric surgery on the responsiveness to subsequent treatments for infertility is not clearly understood at this time’’ (192, 193). 
 
Unfortunately, there are limited studies evaluating the effect of bariatric surgery on fertility outcome. Two systematic reviews assessing reproductive outcome after bariatric surgery published in 2008 and 2009 found very few studies assessing effect on fertility and LBR, although most demonstrate a decreased risk of some complications during pregnancy such as gestational diabetes, hypertensive disorders of pregnancy, and macrosomia (193, 194). However, other studies have suggested a possibly increased risk of small for gestational age singleton births, preterm births, spontaneous preterm births, and possibly increased neonatal mortality (195–197). 
 
A meta-analysis published in 2016 found that the incidence of diagnostic features associated with PCOS significantly decreased after bariatric surgery (46% preoperatively vs. 7% postoperatively, P< .001) as did the incidence of infertility (18% preoperatively vs. 4% postoperatively, P¼ .0009) (198). Two studies assessing the effect of bariatric surgery on IVF in patients who had previously failed IVF found conflicting outcomes. The first study published in 2014 included seven patients who underwent IVF before and after bariatric surgery and found a decrease in the amount of gonadotropin units required for stimulation but no difference in peak estradiol level, number of follicles and oocytes, fertilization rate, or number of top-quality embryos (199). The second larger study published in 2017 included 40 patients and, similar to the previous study, noted a decrease in required gonadotropin units but found an increased number of mature follicles, retrieved oocytes, mature oocytes, fertilization rate, and top-quality embryos. The pregnancy rate after bariatric surgery was found to be 37.5%, and the LBR was 35%. Given that all patients had previously failed IVF, the changes in pregnancy rate and LBR were found to be significant (P< .001) (200). 
 
Because of concerns regarding malabsorption, prepregnancy assessment of a patient’s nutritional status and micronutrient supplementation after bariatric surgery is imperative (193, 194, 201). Delaying pregnancy until 1–2 years after bariatric surgery has been recommended to avoid fetal exposure to nutritional deficiencies from rapid maternal weight loss (193, 202), and the ASMBS recommends waiting 12–18 months (203). Particularly in late reproductive years, the benefits of postponing pregnancy to achieve weight loss must be balanced against the risk of declining fertility with advancing age.  

WEIGHT LOSS INTERVENTION TRIALS AND FERTILITY OUTCOMES 

Three multisite randomized controlled trials (RCTs) have been recently published assessing the effects of weight loss interventions on fertility outcomes. The OWL PCOS study was a two-site RCT that randomized 149 women with PCOS (BMI range, 27–42 kg/m2; median, approximately 35) to one of three arms: oral contraceptive pills (OCPs); lifestyle modification; and combined OCP and lifestyle modification before infertility treatment (9). The lifestyle modification intervention consisted of caloric restriction, behavioral modification, increased physical activity, and weight loss medications (sibutramine or orlistat if the BMI was at least 30 kg/m2). Caloric restriction consisted of prescribed diets centered on meal replacements. In addition, participants consumed two servings of fruit and skim milk per day and three servings of vegetables per day. The diet was designed to create a caloric deficit on the basis of initial weight with at least 15% calories from protein, less than 30% calories from fat, and the remaining calories from carbohydrate. Physical activity included brisk walking or similar aerobic activity 5 days a week with the initial goal of 10 minutes per day, gradually increasing over 4 months to 30–35 minutes per day, for a total activity goal of 150 minutes per week. Women in the lifestyle intervention arms also underwent behavioral modification sessions delivered by trained study coordinators. 
 
These investigators found that women in the lifestyle and combined groups achieved significantly more weight loss compared with those in the OCP group (-6.2 and -6.1 vs. -1.1 kg, respectively; P< .001), although there was a 12%–14% dropout rate for the lifestyle intervention arms. Metabolic parameters improved as did the likelihood of ovulation in the lifestyle and combined groups compared with the OCP group (60% and 67% vs. 46%, respectively; P< .05). However, there were no significant differences in pregnancy or pregnancy loss rates or LBRs (26%, 24%, and 12%, respectively; P¼ .13) between the groups (9). In a post hoc analysis, when patients from both the lifestyle modification group (group 2) and combined group (group 3) were combined and compared with the OCP group (group 1), the probability of live birth bordered statistical significance (P¼ .05) (9). 

The Dutch LIFEstyle study randomized 577 infertile women with a BMI of R29 kg/m2 (median BMI, 36 kg/m2) to 6 months of lifestyle intervention before 18 months of infertility treatment vs. prompt 24 months of infertility treatment (7). The lifestyle intervention consisted of a 6-month structured program including six outpatient visits and four telephone consultations during a 24-week period, with the goal of 5%–10% body weight loss. Women were advised to decrease energy intake by 600 kcal daily while maintaining at least 1,200 kcal per day and were encouraged to engage in moderate-intensity physical activity (target of 10,000 steps per day) with at least 30 minutes of moderate-intensity exercise two or three times per week. They were also provided motivational counseling and developed individualized goals with the assistance of weight management coaches. Similar to the OWL PCOS study, they found significantly greater weight loss in the intervention arm (-4.4 vs. -1.1 kg, P< .001), although there was no difference noted between the groups at 5-year follow-up (204). 
 
The LIFEstyle study reported a 22% dropout rate. However, of those who completed the intervention, 43% achieved weight loss of at least 5% of the initial body weight. The study found that women in the intervention group were significantly less likely to experience a live birth within 24 months after randomization (27% vs. 35%; rate ratio, 0.77; 95% CI, 0.60–0.99). However, when accounting for pregnancies conceived during the 24 months in addition to those delivered within that time frame, there were no significant between-group differences in the LBR. It is notable that the women in the intervention group were significantly more likely to have an unassisted conception compared with those in the control group (26% vs. 16%; rate ratio, 1.61; 95% CI, 1.16–2.24), ultimately requiring fewer fertility treatments. Also worth noting is that participants in the intervention group who achieved the most weight loss had a lower risk of pregnancy complications such as hypertension and preterm birth. A cost-effective analysis of this study demonstrated that lifestyle intervention preceding infertility treatment is less costly but not more effective than prompt infertility treatments regarding LBR (205). 
 
A subsequent Swedish multicenter trial randomized 317 women with BMIs of R30 and <35 kg/m2 (median BMI, approximately 33 kg/m2) to either 16 weeks of weight reduction followed by IVF or immediate IVF treatment (8). The weight reduction intervention aimed to reach a BMI as close to normal as possible and began with 12 weeks of a strict low-calorie liquid formula diet with a daily energy intake of 880 kcal followed by individual visits with a dietician for the reintroduction of solid foods and weight control stabilization. They found that weight reduction in the intervention group was significantly higher than in the control group (-9.44 vs. þ1.19 kg, P< .0001).  
 
Interestingly, as opposed to findings in the previously mentioned studies, the dropout rate for the intervention group was only 4%. This study also did not find a statistically significant difference in overall LBR (29.6% vs. 27.5%, weight loss group vs. control, respectively; P¼ .77). However, similar to the Dutch study, they found a significantly higher rate of spontaneous pregnancy in the weight loss group (11% vs. 3%, P¼ .009) although it is unclear how many women in the immediate IVF group had the opportunity for pregnancy before beginning IVF treatments (8). Two subgroup analyses were performed comparing women with PCOS in the two randomized groups and women who achieved a BMI of %25 kg/m2 in the weight reduction group and similarly found no differences in LBRs. Smaller RCTs and observational studies have reported conflicting evidence for the benefit of lifestyle interventions on fertility outcomes, with most studies either being underpowered to detect a difference or demonstrating no effect on LBR (42, 206–209). Although a post hoc analysis of the LIFEstyle study demonstrated decreased risks of hypertensive pregnancy complications and preterm birth, there were no significant differences in excessive gestational weight gain, gestational diabetes, induction of labor, spontaneous vaginal delivery, or cesarean section (210). A systematic review of interventions for improving fertility in overweight and obese patients published in 2017 included 40 studies and assessed outcome by intervention and study type (46). In the analysis of the RCTs assessing the effect of diet and exercise, there was an improvement noted in the ovulation rate (RR, 4.00; 95% CI, 1.25–12.84) and pregnancy rate (RR, 1.59; 95% CI, 1.01–2.50), but there was no benefit found for unassisted conceptions (RR, 2.20; 95% CI, 0.98–4.93), IVF conceptions (RR, 1.06; 95% CI, 0.53–2.13), or LBR (RR, 1.54; 95% CI, 0.93–2.56). The investigators performed a subanalysis excluding the LIFEstyle study, citing its significant contribution to heterogeneity, and found that diet and exercise offered a statistical advantage for LBR (RR, 1.86; 95% CI, 1.25–2.77). A second meta-analysis published in 2020 included eight RCTs and found that lifestyle programs had no impact on LBR and were possibly associated with an increased risk of miscarriage (RR, 1.50; 95% CI, 1.04–2.16) (211). 
 
Taken together, these data suggest that lifestyle interventions, weight loss medications, and bariatric surgery lead to significant weight loss and may improve chances of unassisted conception; however, their effects on birth outcomes are still unclear. Whereas weight loss intervention trials have not typically demonstrated an improvement in LBR among patients pursuing fertility treatments, some studies have demonstrated reduced pregnancy morbidities, possibly suggesting an increased likelihood of a healthy pregnancy and live birth. In anovulatory women with obesity, studies support implementation of a weight loss intervention for those seeking to improve their chances of unassisted conception and improve the ovulation rate in response to ovulation induction. In obese ovulatory women and in those needing IVF, the intervention trials do not support the implementation of a weight loss intervention for the purpose of improvement in LBR. However, weight loss before IVF may lead to a lower IVF procedural complication rate, and weight loss before pregnancy may decrease the risk of some pregnancy complications. Additional research is needed to further our understanding of maternal and fetal risks and benefits associated with prepregnancy weight loss interventions, particularly because they relate to hypertensive disorders of pregnancy and miscarriage risk.  

BMI THRESHOLDS AND INFERTILITY TREATMENT 

Arbitrary BMI thresholds, below which fertility treatment is permitted and above which fertility treatment is denied until the patient loses weight, have been enacted or contemplated by some programs as well as some national health systems. Proponents of BMI thresholds cite anesthetic and procedural safety during oocyte retrieval and obstetric risk as primary concerns (212–214). They may assume that weight loss is an achievable goal that will lead to improved infertility treatment and obstetric outcomes (215, 216). Challenges in adequately performing retrievals, embryo transfers, inseminations, and ultrasound monitoring can occur in women with obesity (213, 214). Obesity during pregnancy increases a broad spectrum of maternal, fetal, and neonatal risks (23, 114), leading to ethical concerns about causing harm to women with obesity and their offspring (213). Concern about violating the ethical principle of justice by allocating limited resources to at-risk patients with poorer outcomes has been expressed (217, 218). 
 
The Royal Australian and New Zealand College of Obstetricians and Gynaecologists has recommended a BMI threshold of 35 kg/m2 (219), and New Zealand limits access to publicly funded IVF to women with a BMI of <32 kg/m2 (220). In the United Kingdom, the Clinical Commissioning Groups typically set BMI thresholds in the 30–35 kg/m2 range, above which women cannot access publicly funded fertility care (218). In North America, there are no recommended national BMI thresholds. A survey of Canadian IVF centers found that 50% of programs had a declared BMI threshold, which ranged from 35 to 45 kg/m2. The most frequent reason given for having a cutoff was concern about obstetric risk (212). 
 
In the United States, 65% of SART member programs responding to a survey had a declared BMI threshold. Excepting one center with a threshold BMI exceeding 50 kg/m2, the BMI range was 35–45 kg/m2. The most frequent reason given for having a cutoff was anesthetic concern. All large programs (1,000 or more cycles annually) had a formal policy, and a higher percentage of programs in mandated states had a BMI threshold policy compared with nonmandated states. Some programs have additional criteria such as actual weight, neck/abdomen/waist circumference, waste–hip ratio, percentage of body fat, presence of other comorbidities, and inadequate trial transfer (213). Most maternal-fetal medicine and reproductive endocriniology and infertility subspecialists queried in a recent survey favor the establishment of an upper BMI threshold, and over 99% believe that ‘‘an official statement to guide clinicians’’ should be issued by a national professional organization (221). 
 
Opponents of BMI thresholds refer to the American College of Obstetricians and Gynecologists’ stance that ‘‘it is unethical for obstetrician-gynecologists to refuse to accept a patient or decline to continue care that is within their scope of safe practice solely based on an arbitrary BMI cutoff or because the patient has obesity’’ (222). They cite recent data that challenge assumptions about the risks of oocyte retrieval in women with obesity and that triage to lifestyle modification to achieve weight loss before infertility treatment can achieve that goal and improve fertility treatment success rates. They also note that weight loss after bariatric surgery is associated with some improved obstetric outcomes but also an increased risk of certain adverse obstetric outcomes (7, 196, 214, 216). Concern about violating the ethical principles of patient autonomy,  beneficence/nonmaleficence, and justice is prominent among opponents to BMI thresholds (3, 217–219, 222). 
 
Regarding safety concerns, a recent series from a hospital-based IVF program evaluating 256 retrievals in 144 women with a BMI of >40 kg/m2, including 32 retrievals for women with a BMI of >50 kg/m2, suggests that retrievals can be performed safely in women with class 3 and 4 obesity managed in the appropriate clinical setting. The need for abdominal retrieval, conversion from simple mask to laryngeal mask airway oxygenation, or need for an oral or nasal airway was required in less than 7% of retrievals. The use of continuous positive airway pressure therapy to manage oxygen desaturation was required in 18% of women with a BMI of >40 kg/m2. Compared with retrievals with a BMI of <40 kg/ m2, higher doses of anesthetic medications were required, and the duration of the retrieval was approximately 20% longer in the highest BMI categories (214). Findings from this series are encouraging; however, they require validation from additional studies. Table 4 shows the factors favoring and not favoring the adoption of BMI thresholds.

Figure 2


Obesity-FIg2-obesity.jpeg

Table 4


BMI Threshold Pros and Cons

Favoring BMI thresholds Not favoring BMI thresholds
Anesthetic and procedural safety and technical concerns. (213, 214). Preliminary data, requiring validation by additional studies, demonstrates oocyte retrieval in Class 3 and Class 4 obesity can be safely managed in the proper setting (214).
Decreased IVF pregnancy and live birth rates with increasing BMI (72, 223). Access to IVF is permitted in the presence of other factors with decreased pregnancy and live birth rates, such as advanced reproductive age or diminished ovarian reserve (217-219).
Increased maternal, fetal, and neonatal risks related to pregnancy in women with obesity (23, 114). Access to IVF is permitted in the presence of conditions such as hypertension, diabetes, cancer, maternal use of medications that confer maternal, fetal, and neonatal risks (224).
Assumption that weight loss is achievable and will lead to improved infertility treatment and obstetric outcomes (215, 216). Weight loss goals are often not achieved, time to achieve pregnancy is prolonged, and live birth rates are either equivalent or lower in women undergoing pre-treatment lifestyle weight loss intervention vs immediate infertility treatment. Weight loss after bariatric surgery decreases risk of gestational diabetes and macrosomia but increases risk of SGA and preterm delivery (7, 8, 196, 216).
Concern about violating the ethical principle of beneficence/non-maleficence by causing harm to women with obesity and their offspring as a result of fertility treatment and pregnancy (213). Concern about violating the ethical principle of beneficence/non-maleficence by exacerbating underlying psychological suffering due to low self-esteem, anxiety, and depression if treatment is denied. (217, 219).
Concern about violating the ethical principle of justice by allocating limited resources to at risk patients with poorer outcomes (217, 218). Concern about violating the ethical principle of justice by denying choice to procreate to the minority of women with obesity who are infertile, discriminating against ethnic groups with higher obesity prevalence, and being influenced by societal and individual biases towards women with obesity (3, 217-219, 222).
Evidence that weight loss improves likelihood of spontaneous unassisted conception (7, 8). Concern about violating the ethical principle of autonomy by denying obese infertile women the choice to procreate (217).
Note: BMI=body mass index; IVF=in vitro fertilization.
On the basis of available evidence, there is no medical or ethical directive for adopting a society-wide BMI threshold; rather, there is considerable evidence arguing against such a policy. However, there are significant safety concerns that must be acknowledged with increasing BMI, particularly in the case of IVF. In the United States, most oocyte retrievals and other fertility enhancing procedures are conducted in outpatient facilities where endotracheal intubation is not readily available and where the ability to manage procedural complications may be limited. Women with morbid obesity have reduced functional residual capacity and increased oxygen use and desaturate rapidly if they become apneic. Face mask ventilation to maintain adequate oxygenation can be challenging (225), and patients may require oral/nasal airway or continuous positive airway pressure therapy, which may not be available at several clinics. 
 
The outcome data for ambulatory surgery for patients with a BMI between 40 and 50 kg/m2 are limited, and therefore, it is suggested that other factors such as difficult airway, cardiovascular disease (e.g., hypertension), obstructive sleep apnea, and endocrine dysfunction are taken into consideration. Ideally, patients with these comorbidities should be evaluated before the day of surgery (226). Equipment such as operating room tables may not be adequate to support patients with a high BMI. Imaging of the ovaries and cervix in obese patients is often challenging, leading to concerns about being able to safely perform retrievals, embryo transfers, and inseminations. Given these limitations, individual programs may need to adopt program-specific BMI thresholds that should be based solely on the safety and ability to perform oocyte retrievals and other procedures within their clinical environment. Consultation with their supporting anesthesia team is an essential aspect of developing thresholds. Concurrently, consideration of the medical evidence, acknowledgment of potential bias, and respect for the ethical principles of patient autonomy, beneficence, nonmaleficence, and justice should be incorporated into clinic-specific policies.  

SUMMARY 

  • Although obesity increases the risk of infertility, most women and men with obesity are fertile. 
  • Obesity in women is associated with ovulatory dysfunction, reduced ovarian responsiveness to agents that induce ovulation, altered oocyte as well as endometrial function, and lower birth rates after IVF. 
  • Women with obesity are at increased risk of developing maternal and fetal complications during pregnancy. 
  • Men with obesity may exhibit impaired reproductive function. 
  • Lifestyle modification and medical therapy have demonstrated effectiveness in promoting weight loss. 
  • Bariatric surgery in women and men is a significant adjuvant to lifestyle modification and medical therapy for weight loss, but pregnancy in women should be deferred for 1 year postoperatively. 
  • In anovulatory women with obesity, weight loss interventions improve the chance of unassisted conception. 
  • In anovulatory women with obesity, weight loss interventions improve the ovulation rate in response to ovulation induction. However, they have not been shown to improve the LBR. 
  • In ovulatory women with obesity, prepregnancy weight loss interventions have not been shown to improve the outcome of live birth after both non-ART therapy and IVF. 
  • The effect of prepregnancy weight loss interventions on maternal and fetal complications is unclear. 
  • On the basis of available evidence, there is no medical or ethical directive for adopting a society-wide BMI threshold for offering infertility treatment; rather, there is considerable evidence arguing against such a policy. 
  • Before an IVF cycle, women with obesity should be carefully evaluated with a multidisciplinary team to determine the safety of oocyte retrieval under anesthesia, considering 
  • factors such as BMI and comorbidities. 


CONCLUSION 

  • Obesity should not be the sole criteria for denying a patient or couple access to infertility treatment. 
  • Individual programs should be empowered to adopt program-specific BMI thresholds solely on the basis of the ability to safely perform oocyte retrievals and other procedures within their clinical environment. 
  • When obesity increases medical risks, a process of shared decision-making should be undertaken, balancing patient autonomy with nonmaleficence. 
  • Additional research is needed to determine best practices, validate safety data, and optimize access to oocyte retrievals in the setting of class 3 and 4 obesity. 
  • Women with obesity are at increased risk of infertility and of developing maternal and fetal complications during pregnancy. 
  • Prepregnancy counseling for couples with obesity should address the reproductive and maternal–fetal consequences of obesity. 
  • Weight loss intervention trials in women with obesity and infertility have not shown an improvement in the outcome of live birth after treatment. However, weight loss may improve the chance of unassisted conception. 
  • Weight loss intervention trials in women with obesity and infertility often demonstrated a high dropout rate, and thus, consideration should be given to patient desire and readiness to lose weight as well as the potential effect on the overall chances of success with delayed fertility treatment when recommending deferring conception for the purposes of weight loss. 
  • Additional research is needed to further our understanding of the relationship between obesity in men and reproductive function. 
  • Additional research is needed to further our understanding of maternal and fetal risks and benefits associated with prepregnancy weight loss interventions, particularly because they relate to hypertensive disorders of pregnancy and miscarriage risk.  

Acknowledgments:
This report was developed under the direction of the Practice Committees of the American Society for Reproductive Medicine (ASRM) as a service to its members and other practicing clinicians. Although this document reflects appropriate management of a problem encountered in the practice of reproductive medicine, it is not intended to be the only approved standard of practice or to dictate an exclusive course of treatment. Other plans of management may be appropriate, taking into account the needs of the individual patient, available resources, and institutional or clinical practice limitations. The Practice Committee and the Board of Directors of ASRM have approved this report. This document was reviewed by the ASRM members, and their input was considered in the preparation of the final document. The following members of the ASRM Practice Committee participated in the development of this document: Alan Penzias, M.D.; Ricardo Azziz, M.D., M.P.H., M.B.A.; Kristin Bendikson, M.D.; Tommaso Falcone, M.D.; Karl Hansen, M.D., Ph.D.; Micah Hill, D.O.; Sangita Jindal, Ph.D.; Suleena Kalra, M.D., M.S.C.E.; Jennifer Mersereau, M.D.; Richard Reindollar, M.D.; Chevis N. Shannon, Dr.P.H., M.P.H., M.B.A.; Anne Steiner, M.D., M.P.H.; Cigdem Tanrikut, M.D.; Hugh Taylor, M.D.; and Belinda Yauger, M.D. The Practice Committee acknowledges the special contribution of Karl Hansen, M.D., Ph.D.; Emily Jungheim, M.D.; Emily Evans-Hoeker, M.D.; Christina Boots, M.D.; Shayne Plosker, M.D.; Richard Legro, M.D.; and Juanita Henao, M.D., in the preparation of this document. All Committee members disclosed commercial and financial relationships with manufacturers or distributors of goods or services used to treat patients. The members of the Committee who were found to have conflicts of interest on the basis of the relationships disclosed did not participate in the discussion or development of this document.  

REFERENCES 

  1. Collaborators GBDO, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 2017;377:13–27. 
  2. Fryar CD, Carroll MD, Afful J. Prevalence of overweight, obesity, and severe obesity among adults aged 20 and over: United States, 1960–1962 through 2015–2016. NCHS Health E-Stats 2018. 
  3. Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity and severe obesity among adults: United States, 2017-2018. NCHS Data Brief 2020:1–8. 
  4. Deputy NP, Dub B, Sharma AJ. Prevalence and trends in prepregnancy normal weight - 48 States, New York City, and District of Columbia, 2011-2015. MMWR Morb Mortal Wkly Rep 2018;66: 1402–7. 
  5. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: executive summary. Expert panel on the identification, evaluation, and treatment of overweight in adults. Am J Clin Nutr 1998;68:899–917. 
  6. Kim DD, Basu A. Estimating the medical care costs of obesity in the United States: systematic review, meta-analysis, and empirical analysis. Value Health 2016;19:602–13. 
  7. Mutsaerts MA, van Oers AM, Groen H, Burggraaff JM, Kuchenbecker WK, Perquin DA, et al. Randomized trial of a lifestyle program in obese infertile women. N Engl J Med 2016;374:1942–53. 
  8. Einarsson S, Bergh C, Friberg B, Pinborg A, Klajnbard A, Karlstrom P, et al. Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial. Hum Reprod 2017;32:1621–30. 
  9. Legro RS, Dodson WC, Kris-Etherton PM, Kunselman AR, Stetter CM, Williams NI, et al. Randomized controlled trial of preconception interventions in infertile women with polycystic ovary syndrome. J Clin Endocrinol Metab 2015;100:4048–58. 
  10. Willett WC, Manson JE, Stampfer MJ, Colditz GA, Rosner B, Speizer FE, et al. Weight, weight change, and coronary heart disease in women. Risk within the ‘normal’ weight range. J Am Med Assoc 1995;273:461–5. 
  11. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 1995;122: 481–6. 
  12. Huang Z, Willett WC, Manson JE, Rosner B, Stampfer MJ, Speizer FE, et al. Body weight, weight change, and risk for hypertension in women. Ann Intern Med 1998;128:81–8. 
  13. Maclure KM, Hayes KC, Colditz GA, Stampfer MJ, Speizer FE, Willett WC. Weight, diet, and the risk of symptomatic gallstones in middle-aged women. N Engl J Med 1989;321:563–9. 
  14. Huang Z, Hankinson SE, Colditz GA, Stampfer MJ, Hunter DJ, Manson JE, et al. Dual effects of weight and weight gain on breast cancer risk. J Am Med Assoc 1997;278:1407–11. 
  15. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K. Body fatness and cancer–viewpoint of the IARC working group. N Engl J Med 2016;375:794–8. 
  16. Walker SP, Rimm EB, Ascherio A, Kawachi I, Stampfer MJ, Willett WC. Body size and fat distribution as predictors of stroke among US men. Am J Epidemiol 1996;144:1143–50. 
  17. Rich-Edwards JW, Goldman MB, Willett WC, Hunter DJ, Stampfer MJ, Colditz GA, et al. Adolescent body mass index and infertility caused by ovulatory disorder. Am J Obstet Gynecol 1994;171:171–7. 
  18. Quetelet A. Physique sociale ou essai sur le d'eveloppement des facult'es de l’homme. Brussels, Belgium: C. Muquardt; 1869. 
  19. World Health Organization. WHO Technical Report Series 894. Available at: https://books.google.com/books?hl¼en&lr¼&id¼AvnqOsqv9doC&oi¼fnd&pg¼PA1&dq¼WHOþTechnicalþReportþSeriesþ894&ots¼6WF2ao_V8P&sig¼x3I66StMIP9UkonTtJFRoEXrVfw#v¼onepage&q¼WHO%20Technical%20Report%20Series%20894&f¼false.  Accessed  June 2, 2021. 
  20. Willett WC, Dietz WH, Colditz GA. Guidelines for healthy weight. N Engl J Med 1999;341:427–34. 
  21. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363:157–63. 
  22. Gaskins AJ, Rich-Edwards JW, Missmer SA, Rosner B, Chavarro JE. Association of fecundity with changes in adult female weight. Obstet Gynecol 2015;126:850–8. 
  23. ACOG Practice Bulletin No 156: Obesity in pregnancy. Obstet Gynecol 2015;126:112–26. 
  24. Craig JR, Jenkins TG, Carrell DT, Hotaling JM. Obesity, male infertility, and the sperm epigenome. Fertil Steril 2017;107:848–59. 
  25. Broughton DE, Moley KH. Obesity and female infertility: potential mediators of obesity's impact. Fertil Steril 2017;107:840–7. 
  26. Azziz R, Adashi EY. Stein and Leventhal: 80 years on. Am J Obstet Gynecol 2016;214:247.e1–11. 
  27. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935;29:181–91. 
  28. Rogers J, Mitchell GW Jr. The relation of obesity to menstrual disturbances. N Engl J Med 1952;247:53–5. 
  29. Alvarez-Blasco F, Botella-Carretero JI, San Millan JL, Escobar-Morreale HF. Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women. Arch Intern Med 2006;166:2081–6. 
  30. Escobar-Morreale HF, Santacruz E, Luque-Ramirez M, Botella Carretero JI. Prevalence of 'obesity-associated gonadal dysfunction' in severely obese men and women and its resolution after bariatric surgery: a systematic review and meta-analysis. Hum Reprod Update 2017;23:390–408. 
  31. Polotsky AJ, Hailpern SM, Skurnick JH, Lo JC, Sternfeld B, Santoro N. Association of adolescent obesity and lifetime nulliparity–the Study of Women's Health Across the Nation (SWAN). Fertil Steril 2010;93:2004–11. 
  32. Castillo-Martinez L, Lopez-Alvarenga JC, Villa AR, Gonzalez-Barranco J. Menstrual cycle length disorders in 18- to 40-y-old obese women. Nutrition 2003;19:317–20. 
  33. Hartz AJ, Barboriak PN, Wong A, Katayama KP, Rimm AA. The association of obesity with infertility and related menstural abnormalities in women. Int J Obes 1979;3:57–73. 
  34. Legro RS, Dodson WC, Gnatuk CL, Estes SJ, Kunselman AR, Meadows JW, et al. Effects of gastric bypass surgery on female reproductive function. J Clin Endocrinol Metab 2012;97:4540–8. 
  35. Bhandari S, Ganguly I, Bhandari M, Agarwal P, Singh A, Gupta N, et al. Effect of sleeve gastrectomy bariatric surgery-induced weight loss on serum AMH levels in reproductive aged women. Gynecol Endocrinol 2016;32: 799–802. 
  36. Lake JK, Power C, Cole TJ. Women's reproductive health: the role of body mass index in early and adult life. Int J Obes Relat Metab Disord 1997;21: 432–8. 
  37. Grodstein F, Goldman MB, Cramer DW. Body mass index and ovulatory infertility. Epidemiology 1994;5:247–50. 
  38. Kuchenbecker WK, Groen H, Zijlstra TM, Bolster JH, Slart RH, van der Jagt EJ, et al. The subcutaneous abdominal fat and not the intraabdominal fat compartment is associated with anovulation in women with obesity and infertility. J Clin Endocrinol Metab 2010;95:2107–12. 
  39. Zaadstra BM, Seidell JC, Van Noord PA, te Velde ER, Habbema JD, Vrieswijk B, et al. Fat and female fecundity: prospective study of effect of body fat distribution on conception rates. Br Med J 1993;306:484–7. 
  40. Yildiz BO, Knochenhauer ES, Azziz R. Impact of obesity on the risk for polycystic ovary syndrome. J Clin Endocrinol Metab 2008;93:162–8. 
  41. Legro RS. Obesity and PCOS: implications for diagnosis and treatment. Semin Reprod Med 2012;30:496–506. 
  42. Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod 1998;13:1502–5. 
  43. Palomba S, Falbo A, Giallauria F, Russo T, Rocca M, Tolino A, et al. Six weeks of structured exercise training and hypocaloric diet increases the probability of ovulation after clomiphene citrate in overweight and obese patients with polycystic ovary syndrome: a randomized controlled trial. Hum Reprod 2010;25:2783–91. 
  44. Kumar P, Arora S. Orlistat in polycystic ovarian syndrome reduces weight with improvement in lipid profile and pregnancy rates. J Hum Reprod Sci 2014;7:255–61. 
  45. Thomson RL, Buckley JD, Noakes M, Clifton PM, Norman RJ, Brinkworth GD. The effect of a hypocaloric diet with and without exercise training on body composition, cardiometabolic risk profile, and reproductive function in overweight and obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 2008;93:3373–80. 
  46. Best D, Avenell A, Bhattacharya S. How effective are weight-loss interventions for improving fertility in women and men who are overweight or obese? A systematic review and meta-analysis of the evidence. Hum Reprod Update 2017;23:681–705. 
  47. Small CM, Manatunga AK, Marcus M. Validity of self-reported menstrual cycle length. Ann Epidemiol 2007;17:163–70. 
  48. Santoro N, Lasley B, McConnell D, Allsworth J, Crawford S, Gold EB, 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;89:2622–31. 
  49. Jain A, Polotsky AJ, Rochester D, Berga SL, Loucks T, Zeitlian G, et al. Pulsatile luteinizing hormone amplitude and progesterone metabolite excretion are reduced in obese women. J Clin Endocrinol Metab 2007;92: 2468–73. 
  50. Brewer CJ, Balen AH. The adverse effects of obesity on conception and implantation. Reproduction 2010;140:347–64. 
  51. Pasquali R, Pelusi C, Genghini S, Cacciari M, Gambineri A. Obesity and reproductive disorders in women. Hum Reprod Update 2003;9:359–72. 
  52. Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 2012;33:981–1030. 
  53. Imani B, Eijkemans MJ, te Velde ER, Habbema JD, Fauser BC. A nomogram to predict the probability of live birth after clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. Fertil Steril 2002;77:91–7. 
  54. Legro RS, Brzyski RG, Diamond MP, Coutifaris C, Schlaff WD, Alvero R, et al. The pregnancy in polycystic ovary syndrome II study: baseline characteristics and effects of obesity from a multicenter randomized clinical trial. Fertil Steril 2014;101:258–69.e8. 
  55. Souter I, Baltagi LM, Kuleta D, Meeker JD, Petrozza JC. Women, weight, and fertility: the effect of body mass index on the outcome of superovulation/intrauterine insemination cycles. Fertil Steril 2011; 95:1042–7. 
  56. Fedorcsak P, Dale PO, Storeng R, Ertzeid G, Bjercke S, Oldereid N, et al. Impact of overweight and underweight on assisted reproduction treatment. Hum Reprod 2004;19:2523–8. 
  57. Shah DK, Missmer SA, Berry KF, Racowsky C, Ginsburg ES. Effect of obesity on oocyte and embryo quality in women undergoing in vitro fertilization. Obstet Gynecol 2011;118:63–70. 
  58. Moragianni VA, Jones SM, Ryley DA. The effect of body mass index on the outcomes of first assisted reproductive technology cycles. Fertil Steril 2012; 98:102–8. 
  59. Wang JX, Davies M, Norman RJ. Body mass and probability of pregnancy during assisted reproduction treatment: retrospective study. Br Med J 2000;321:1320–1. 
  60. Pinborg A, Gaarslev C, Hougaard CO, Nyboe Andersen A, Andersen PK, Boivin J, et al. Influence of female bodyweight on IVF outcome: a longitudinal multicentre cohort study of 487 infertile couples. Reprod Biomed Online 2011;23:490–9. 
  61. Robker RL, Akison LK, Bennett BD, Thrupp PN, Chura LR, Russell DL, et al. Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women. J Clin Endocrinol Metab 2009;94:1533–40. 
  62. Jungheim ES, Macones GA, Odem RR, Patterson BW, Lanzendorf SE, Ratts VS, et al. Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization. Fertil Steril 2011;95:1970–4. 
  63. Leary C, Leese HJ, Sturmey RG. Human embryos from overweight and obese women display phenotypic and metabolic abnormalities. Hum Reprod 2015;30:122–32. 
  64. Marquard KL, Stephens SM, Jungheim ES, Ratts VS, Odem RR, Lanzendorf S, et al. Polycystic ovary syndrome and maternal obesity affect oocyte size in in vitro fertilization/intracytoplasmic sperm injection cycles. Fertil Steril 2011;95:2146–9.e1. 
  65. Zhang J, Liu H, Mao X, Chen Q, Fan Y, Xiao Y, et al. Effect of body mass index on pregnancy outcomes in a freeze-all policy: an analysis of 22,043 first autologous frozen-thawed embryo transfer cycles in China. BMC Med 2019;17:114. 
  66. Orvieto R, Meltcer S, Nahum R, Rabinson J, Anteby EY, Ashkenazi J. The influence of body mass index on in vitro fertilization outcome. Int J Gynaecol Obstet 2009;104:53–5. 
  67. Depalo R, Garruti G, Totaro I, Panzarino M, Vacca MP, Giorgino F, et al. Oocyte morphological abnormalities in overweight women undergoing in vitro fertilization cycles. Gynecol Endocrinol 2011;27:880–4. 
  68. Metwally M, Cutting R, Tipton A, Skull J, Ledger WL, Li TC. Effect of increased body mass index on oocyte and embryo quality in IVF patients. Reprod Biomed Online 2007;15:532–8. 
  69. Kudesia R, Wu H, Hunter Cohn K, Tan L, Lee JA, Copperman AB, et al. The effect of female body mass index on in vitro fertilization cycle outcomes: a multi-center analysis. J Assist Reprod Genet 2018;35:2013–23. 
  70. Bartolacci A, Buratini J, Moutier C, Guglielmo MC, Novara PV, Brambillasca F, et al. Maternal body mass index affects embryo morphokinetics: a time-lapse study. J Assist Reprod Genet 2019;36:1109–16. 
  71. Goldman KN, Hodes-Wertz B, McCulloh DH, Flom JD, Grifo JA. Association of body mass index with embryonic aneuploidy. Fertil Steril 2015;103:744– 8. 
  72. Provost MP, Acharya KS, Acharya CR, Yeh JS, Steward RG, Eaton JL, et al. Pregnancy outcomes decline with increasing body mass index: analysis of 239,127 fresh autologous in vitro fertilization cycles from the 2008-2010 Society for Assisted Reproductive Technology registry. Fertil Steril 2016; 105:663–9. 
  73. Kawwass JF, Kulkarni AD, Hipp HS, Crawford S, Kissin DM, Jamieson DJ. Extremities of body mass index and their association with pregnancy outcomes in women undergoing in vitro fertilization in the United States. Fertil Steril 2016;106:1742–50. 
  74. Goldman RH, Farland LV, Thomas AM, Zera CA, Ginsburg ES. The combined impact of maternal age and body mass index on cumulative live birth following in vitro fertilization. Am J Obstet Gynecol 2019;221:617.e1–13. 
  75. Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007;356:551–66. 
  76. Luzzo KM, Wang Q, Purcell SH, Chi M, Jimenez PT, Grindler N, et al. High fat diet induced developmental defects in the mouse: oocyte meiotic aneuploidy and fetal growth retardation/brain defects. PLoS One 2012;7: e49217. 
  77. Jungheim ES, Schoeller EL, Marquard KL, Louden ED, Schaffer JE, Moley KH. Diet-induced obesity model: abnormal oocytes and persistent growth abnormalities in the offspring. Endocrinology 2010;151: 4039–46. 
  78. Reynolds KA, Boudoures AL, Chi MM, Wang Q, Moley KH. Adverse effects of obesity and/or high-fat diet on oocyte quality and metabolism are not reversible with resumption of regular diet in mice. Reprod Fertil Dev 2015;27:716–24. 
  79. Boots CE, Boudoures A, Zhang W, Drury A, Moley KH. Obesity-induced oocyte mitochondrial defects are partially prevented and rescued by supplementation with co-enzyme Q10 in a mouse model. Hum Reprod 2016;31:2090–7. 
  80. Boudoures AL, Chi M, Thompson A, Zhang W, Moley KH. The effects of voluntary exercise on oocyte quality in a diet-induced obese murine model. Reproduction 2016;151:261–70. 
  81. Luke B, Brown MB, Stern JE, Missmer SA, Fujimoto VY, Leach R. Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates. Hum Reprod 2011;26:245–52. 
  82. Jungheim ES, Schon SB, Schulte MB, DeUgarte SA, Fowler SA, Tuuli MG. IVF outcomes in obese donor oocyte recipients: a systematic review and meta-analysis. Hum Reprod 2013;28:2720–7. 
  83. Argenta P, Svendsen C, Elishaev E, Gloyeske N, Geller MA, Edwards RP, et al. Hormone receptor expression patterns in the endometrium of asymptomatic morbidly obese women before and after bariatric surgery. Gynecol Oncol 2014;133:78–82. 
  84. Bellver J, Martínez-Conejero JA, Labarta E, Alam'a P, Melo MA, Remohí J, et al. Endometrial gene expression in the window of implantation is altered in obese women especially in association with polycystic ovary syndrome. Fertil Steril 2011;95:2335–41. 
  85. Mulders AG, Laven JS, Eijkemans MJ, Hughes EG, Fauser BC. Patient predictors for outcome of gonadotrophin ovulation induction in women with normogonadotrophic anovulatory infertility: a meta-analysis. Hum Reprod Update 2003;9:429–49. 
  86. Wang JX, Davies MJ, Norman RJ. Obesity increases the risk of spontaneous abortion during infertility treatment. Obes Res 2002;10:551–4. 
  87. Rittenberg V, Seshadri S, Sunkara SK, Sobaleva S, Oteng-Ntim E, El-Toukhy T. Effect of body mass index on IVF treatment outcome: an updated systematic review and meta-analysis. Reprod Biomed Online 2011; 23:421–39. 
  88. Rittenberg V, Sobaleva S, Ahmad A, Oteng-Ntim E, Bolton V, Khalaf Y, et al. Influence of BMI on risk of miscarriage after single blastocyst transfer. Hum Reprod 2011;26:2642–50. 
  89. Metwally M, Ong KJ, Ledger WL, Li TC. Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception? A meta-analysis of the evidence. Fertil Steril 2008;90:714–26. 
  90. Zhang D, Zhu Y, Gao H, Zhou B, Zhang R, Wang T, et al. Overweight and obesity negatively affect the outcomes of ovarian stimulation and in vitro fertilisation: a cohort study of 2628 Chinese women. Gynecol Endocrinol 2010;26:325–32. 
  91. Fontenelle LC, Feitosa MM, Severo JS, Freitas TE, Morais JB, Torres-Leal FL, et al. Thyroid function in human obesity: underlying mechanisms. Horm Metab Res 2016;48:787–94. 
  92. van den Boogaard E, Vissenberg R, Land JA, van Wely M, van der Post JA, Goddijn M, et al. Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. Hum Reprod Update 2011;17:605–19. 
  93. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444:840–6. 
  94. Tennant PW, Bilous RW, Prathapan S, Bell R. Risk and recurrence of serious adverse outcomes in the first and second pregnancies of women with preexisting diabetes. Diabetes Care 2015;38:610–9. 
  95. S'ainz N, Barrenetxe J, Moreno-Aliaga MJ, Martínez JA. Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism 2015;64:35–46. 
  96. Tessier DR, Ferraro ZM, Gruslin A. Role of leptin in pregnancy: consequences of maternal obesity. Placenta 2013;34:205–11. 
  97. P'erez-P'erez A, Toro A, Vilarin~o-García T, Maymo' J, Guadix P, Duen~as JL, et al. Leptin action in normal and pathological pregnancies. J Cell Mol Med 2018;22:716–27. 
  98. Hohos NM, Skaznik-Wikiel ME. High-fat diet and female fertility. Endocrinology 2017;158:2407–19. 
  99. Lee SJ, Shin SW. Mechanisms, pathophysiology, and management of obesity. N Engl J Med 2017;376:1491–2. 
  100. Levine LD, Holland TL, Kim K, Sjaarda LA, Mumford SL, Schisterman EF. The role of aspirin and inflammation on reproduction: the EAGeR trial 1. Can J Physiol Pharmacol 2019;97:187–92. 
  101. Ogilvie RP, Patel SR. The epidemiology of sleep and obesity. Sleep Health 2017;3:383–8. 
  102. Bonde JP, Jorgensen KT, Bonzini M, Palmer KT. Miscarriage and occupational activity: a systematic review and meta-analysis regarding shift work, working hours, lifting, standing, and physical workload. Scand J Work Environ Health 2013;39:325–34. 
  103. Willis SK, Hatch EE, Wise LA. Sleep and female reproduction. Curr Opin Obstet Gynecol 2019;31:222–7. 
  104. Toffol E, Koponen P, Partonen T. Miscarriage and mental health: results of two population-based studies. Psychiatry Res 2013;205:151–8. 
  105. Rai R, Regan L. Recurrent miscarriage. Lancet 2006;368:601–11. 
  106. Avila C, Holloway AC, Hahn MK, Morrison KM, Restivo M, Anglin R, et al. An overview of links between obesity and mental health. Curr Obes Rep 2015;4:303–10. 
  107. Boots C, Stephenson MD. Does obesity increase the risk of miscarriage in spontaneous conception: a systematic review. Semin Reprod Med 2011; 29:507–13. 
  108. Zhou Y, Li H, Zhang Y, Zhang L, Liu J, Liu J. Association of maternal obesity in early pregnancy with adverse pregnancy outcomes: a Chinese prospective cohort analysis. Obesity (Silver Spring) 2019;27: 1030–6. 
  109. Cavalcante MB, Sarno M, Peixoto AB, Araujo Ju'nior E, Barini R. Obesity and recurrent miscarriage: a systematic review and meta-analysis. J Obstet Gynaecol Res 2019;45:30–8. 
  110. Bellver J, Pellicer A, García-Velasco JA, Ballesteros A, Remohí J, Meseguer M. Obesity reduces uterine receptivity: clinical experience from 9,587 first cycles of ovum donation with normal weight donors. Fertil Steril 2013;100:1050–8. 
  111. Provost MP, Acharya KS, Acharya CR, Yeh JS, Steward RG, Eaton JL, et al. Pregnancy outcomes decline with increasing recipient body mass index: an analysis of 22,317 fresh donor/recipient cycles from the 2008-2010 Society for Assisted Reproductive Technology Clinic Outcome Reporting System registry. Fertil Steril 2016;105:364–8. 
  112. Boots CE, Bernardi LA, Stephenson MD. Frequency of euploid miscarriage is increased in obese women with recurrent early pregnancy loss. Fertil Steril 2014;102:455–9. 
  113. Lee J, Bernardi LA, Boots CE. The association of euploid miscarriage with obesity. F S Rep 2020;1:42–8. 
  114. Kim SS, Zhu Y, Grantz KL, Hinkle SN, Chen Z, Wallace ME, et al. Obstetric and neonatal risks among obese women without chronic disease. Obstet Gynecol 2016;128:104–12. 
  115. Denison FC, Aedla NR, Keag O, Hor K, Reynolds RM, Milne A, Diamond A. Care of women with obesity in pregnancy: Green-top Guideline No. 72. BJOG 2019;126:62–106. 
  116. Rolland M, Le Moal J, Wagner V, Roy'ere D, De Mouzon J. Decline in semen concentration and morphology in a sample of 26,609 men close to general population between 1989 and 2005 in France. Hum Reprod 2013;28: 462–70. 
  117. Sengupta P, Borges E Jr, Dutta S, Krajewska-Kulak E. Decline in sperm count in European men during the past 50 years. Hum Exp Toxicol 2018; 37:247–55. 
  118. Dandona P, Dhindsa S. Update: hypogonadotropic hypogonadism in type 2 diabetes and obesity. J Clin Endocrinol Metab 2011;96:2643–51. 
  119. Luboshitzky R, Lavie L, Shen-Orr Z, Herer P. Altered luteinizing hormone and testosterone secretion in middle-aged obese men with obstructive sleep apnea. Obes Res 2005;13:780–6. 
  120. Cabler S, Agarwal A, Flint M, du Plessis SS. Obesity: modern man's fertility nemesis. Asian J Androl 2010;12:480–9. 
  121. Sallm'en M, Sandler DP, Hoppin JA, Blair A, Baird DD. Reduced fertility among overweight and obese men. Epidemiology 2006;17:520–3. 
  122. Pasquali R. Obesity and androgens: facts and perspectives. Fertil Steril 2006;85:1319–40. 
  123. Hammoud AO, Wilde N, Gibson M, Parks A, Carrell DT, Meikle AW. Male obesity and alteration in sperm parameters. Fertil Steril 2008;90:2222–5. 
  124. Bakos HW, Henshaw RC, Mitchell M, Lane M. Paternal body mass index is associated with decreased blastocyst development and reduced live birth rates following assisted reproductive technology. Fertil Steril 2011;95: 1700–4. 
  125. Relwani R, Berger D, Santoro N, Hickmon C, Nihsen M, Zapantis A, et al. Semen parameters are unrelated to BMI but vary with SSRI use and prior urological surgery. Reprod Sci 2011;18:391–7. 
  126. Umul M, Kose SA, Bilen E, Altuncu AG, Oksay T, Guney M. Effect of increasing paternal body mass index on pregnancy and live birth rates in couples undergoing intracytoplasmic sperm injection. Andrologia 2015; 47:360–4. 
  127. Sermondade N, Faure C, Fezeu L, Shayeb AG, Bonde JP, Jensen TK, et al. BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis. Hum Reprod Update 2013;19:221–31. 
  128. Braga DP, Halpern G, Figueira Rde C, Setti AS, Iaconelli A Jr, Borges E Jr. Food intake and social habits in male patients and its relationship to intra-cytoplasmic sperm injection outcomes. Fertil Steril 2012;97:53–9. 
  129. Hammiche F, Laven JS, Twigt JM, Boellaard WP, Steegers EA, Steegers-Theunissen RP. Body mass index and central adiposity are associated with sperm quality in men of subfertile couples. Hum Reprod 2012;27: 2365–72. 
  130. Bieniek JM, Kashanian JA, Deibert CM, Grober ED, Lo KC, Brannigan RE, et al. Influence of increasing body mass index on semen and reproductive hormonal parameters in a multi-institutional cohort of subfertile men. Fertil Steril 2016;106:1070–5. 
  131. Andersen JM, Herning H, Aschim EL, Hjelmesæth J, Mala T, Hanevik HI, et al. Body mass index is associated with impaired semen characteristics and reduced levels of anti-Mullerian hormone across a wide weight range. PLoS One 2015;10:e0130210. 
  132. Thomsen L, Humaidan P, Bungum L, Bungum M. The impact of male overweight on semen quality and outcome of assisted reproduction. Asian J Androl 2014;16:1–6. 
  133. Eisenberg ML, Kim S, Chen Z, Sundaram R, Schisterman EF, Buck Louis GM. The relationship between male BMI and waist circumference on semen quality: data from the LIFE study. Hum Reprod 2014;29: 193–200. 
  134. Al-Ali BM, Gutschi T, Pummer K, Zigeuner R, Brookman-May S, Wieland WF, et al. Body mass index has no impact on sperm quality but on reproductive hormones levels. Andrologia 2014;46:106–11. 
  135. Duits FH, van Wely M, van der Veen F, Gianotten J. Healthy overweight male partners of subfertile couples should not worry about their semen quality. Fertil Steril 2010;94:1356–9. 
  136. Lotti F, Corona G, Colpi GM, Filimberti E, Degli Innocenti S, Mancini M, et al. Elevated body mass index correlates with higher seminal plasma interleukin 8 levels and ultrasonographic abnormalities of the prostate in men attending an andrology clinic for infertility. J Endocrinol Invest 2011;34: e336–42. 
  137. MacDonald AA, Herbison GP, Showell M, Farquhar CM. The impact of body mass index on semen parameters and reproductive hormones in human males: a systematic review with meta-analysis. Hum Reprod Update 2010;16:293–311. 
  138. Povey AC, Clyma JA, McNamee R, Moore HD, Baillie H, Pacey AA, et al. Modifiable and non-modifiable risk factors for poor semen quality: a case-referent study. Hum Reprod 2012;27:2799–806. 
  139. Vermeulen A, Kaufman JM, Deslypere JP, Thomas G. Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men. J Clin Endocrinol Metab 1993;76:1140–6. 
  140. Giagulli VA, Kaufman JM, Vermeulen A. Pathogenesis of the decreased androgen levels in obese men. J Clin Endocrinol Metab 1994;79:997– 1000. 
  141. Palmer NO, Bakos HW, Fullston T, Lane M. Impact of obesity on male fertility, sperm function and molecular composition. Spermatogenesis 2012;2:253–63. 
  142. Chavarro JE, Toth TL, Wright DL, Meeker JD, Hauser R. Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic. Fertil Steril 2010;93:2222–31. 
  143. Dupont C, Faure C, Sermondade N, Boubaya M, Eustache F, Cl'ement P, et al. Obesity leads to higher risk of sperm DNA damage in infertile patients. Asian J Androl 2013;15:622–5. 
  144. Fariello RM, Pariz JR, Spaine DM, Cedenho AP, Bertolla RP, Fraietta R. Association between obesity and alteration of sperm DNA integrity and mitochondrial activity. BJU Int 2012;110:863–7. 
  145. La Vignera S, Condorelli RA, Vicari E, Calogero AE. Negative effect of increased body weight on sperm conventional and nonconventional flow cytometric sperm parameters. J Androl 2012;33:53–8. 
  146. Rybar R, Kopecka V, Prinosilova P, Markova P, Rubes J. Male obesity and age in relationship to semen parameters and sperm chromatin integrity. Andrologia 2011;43:286–91. 
  147. Tunc O, Bakos HW, Tremellen K. Impact of body mass index on seminal oxidative stress. Andrologia 2011;43:121–8. 
  148. Soubry A, Guo L, Huang Z, Hoyo C, Romanus S, Price T, et al. Obesity-related DNA methylation at imprinted genes in human sperm: results from the TIEGER study. Clin Epigenetics 2016;8:51. 
  149. Keltz J, Zapantis A, Jindal SK, Lieman HJ, Santoro N, Polotsky AJ. Overweight men: clinical pregnancy after ART is decreased in IVF but not in ICSI cycles. J Assist Reprod Genet 2010;27:539–44. 
  150. Colaci DS, Afeiche M, Gaskins AJ, Wright DL, Toth TL, Tanrikut C, et al. Men's body mass index in relation to embryo quality and clinical outcomes in couples undergoing in vitro fertilization. Fertil Steril 2012;98:1193–9.e1. 
  151. Merhi ZO, Keltz J, Zapantis A, Younger J, Berger D, Lieman HJ, et al. Male adiposity impairs clinical pregnancy rate by in vitro fertilization without affecting day 3 embryo quality. Obesity (Silver Spring) 2013;21: 1608–12. 
  152. Ramasamy R, Bryson C, Reifsnyder JE, Neri Q, Palermo GD, Schlegel PN. Overweight men with nonobstructive azoospermia have worse pregnancy outcomes after microdissection testicular sperm extraction. Fertil Steril 2013;99:372–6. 
  153. Campbell JM, Lane M, Owens JA, Bakos HW. Paternal obesity negatively affects male fertility and assisted reproduction outcomes: a systematic review and meta-analysis. Reprod Biomed Online 2015;31:593–604. 
  154. Mushtaq R, Pundir J, Achilli C, Naji O, Khalaf Y, El-Toukhy T. Effect of male body mass index on assisted reproduction treatment outcome: an updated systematic review and meta-analysis. Reprod Biomed Online 2018;36: 459–71. 
  155. Jensen TK, Andersson AM, Jørgensen N, Andersen AG, Carlsen E, Petersen JH, et al. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril 2004;82:863–70. 
  156. Teerds KJ, de Rooij DG, Keijer J. Functional relationship between obesity and male reproduction: from humans to animal models. Hum Reprod Update 2011;17:667–83. 
  157. HOakonsen LB, Thulstrup AM, Aggerholm AS, Olsen J, Bonde JP, Andersen CY, et al. Does weight loss improve semen quality and reproductive hormones? Results from a cohort of severely obese men. Reprod Health 2011;8:24. 
  158. Zumoff B, Strain GW, Miller LK, Rosner W, Senie R, Seres DS, et al. Plasma free and non-sex-hormone-binding-globulin-bound testosterone are decreased in obese men in proportion to their degree of obesity. J Clin Endocrinol Metab 1990;71:929–31. 
  159. Pitteloud N, Hardin M, Dwyer AA, Valassi E, Yialamas M, Elahi D, et al. Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab 2005;90:2636–41. 
  160. Stewart TM, Liu DY, Garrett C, Jørgensen N, Brown EH, Baker HW. Associations between andrological measures, hormones and semen quality in fertile Australian men: inverse relationship between obesity and sperm output. Hum Reprod 2009;24:1561–8. 
  161. Jarow JP, Kirkland J, Koritnik DR, Cefalu WT. Effect of obesity and fertility status on sex steroid levels in men. Urology 1993;42:171–4. 
  162. Baker HW. Reproductive effects of nontesticular illness. Endocrinol Metab Clin North Am 1998;27:831–50. 
  163. Schneider J, Bradlow HL, Strain G, Levin J, Anderson K, Fishman J. Effects of obesity on estradiol metabolism: decreased formation of nonuterotropic metabolites. J Clin Endocrinol Metab 1983;56:973–8. 
  164. Isidori AM, Caprio M, Strollo F, Moretti C, Frajese G, Isidori A, et al. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab 1999;84:3673–80. 
  165. Wake DJ, Strand M, Rask E, Westerbacka J, Livingstone DE, Soderberg S, et al. Intra-adipose sex steroid metabolism and body fat distribution in idiopathic human obesity. Clin Endocrinol 2007;66:440–6. 
  166. Hofny ER, Ali ME, Abdel-Hafez HZ, Kamal Eel-D, Mohamed EE, Abd El-Azeem HG, et al. Semen parameters and hormonal profile in obese fertile and infertile males. Fertil Steril 2010;94:581–4. 
  167. Jung A, Schill WB. Male infertility. Current life style could be responsible for infertility. MMW Fortschr Med 2000;142:31–3. 
  168. Garolla A, Torino M, Miola P, Caretta N, Pizzol D, Menegazzo M, et al. Twenty-four-hour monitoring of scrotal temperature in obese men and men with a varicocele as a mirror of spermatogenic function. Hum Reprod 2015;30:1006–13. 
  169. Mulcahy JJ. Scrotal hypothermia and the infertile man. J Urol 1984;132: 469–70. 
  170. Kaukua J, Pekkarinen T, Sane T, Mustajoki P. Sex hormones and sexual function in obese men losing weight. Obes Res 2003;11:689–94. 
  171. Moran LJ, Brinkworth GD, Martin S, Wycherley TP, Stuckey B, Lutze J, et al. Long-term effects of a randomised controlled trial comparing high protein or high carbohydrate weight loss diets on testosterone, SHBG, erectile and urinary function in overweight and obese men. PLoS One 2016;11: e0161297. 
  172. Collins CE, Jensen ME, Young MD, Callister R, Plotnikoff RC, Morgan PJ. Improvement in erectile function following weight loss in obese men: the SHED-IT randomized controlled trial. Obes Res Clin Pract 2013;7: e450–4. 
  173. Silva AB, Sousa N, Azevedo LF, Martins C. Physical activity and exercise for erectile dysfunction: systematic review and meta-analysis. Br J Sports Med 2017;51:1419–24. 
  174. El Bardisi H, Majzoub A, Arafa M, AlMalki A, Al Said S, Khalafalla K, et al. Effect of bariatric surgery on semen parameters and sex hormone concentrations: a prospective study. Reprod Biomed Online 2016;33: 606–11. 
  175. Samavat J, Cantini G, Lotti F, Di Franco A, Tamburrino L, Degl'Innocenti S, et al. Massive weight loss obtained by bariatric surgery affects semen quality in morbid male obesity: a preliminary prospective double-armed study. Obes Surg 2018;28:69–76. 
  176. Carette C, Levy R, Eustache F, Baron G, Coupaye M, Msika S, et al. Changes in total sperm count after gastric bypass and sleeve gastrectomy: the BAR-IASPERM prospective study. Surg Obes Relat Dis 2019;15:1271–9. 
  177. Caldero'n B, Huerta L, Galindo J, Gonz'alez Casbas JM, Escobar-Morreale HF, Martín-Hidalgo A, et al. Lack of improvement of sperm characteristics in obese males after obesity surgery despite the beneficial changes observed in reproductive hormones. Obes Surg 2019;29:2045–50. 
  178. Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, et al. Pharmacological management of obesity: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015;100: 342–62. 
  179. Aronne LJ, Wadden TA, Peterson C, Winslow D, Odeh S, Gadde KM. Evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults. Obesity (Silver Spring) 2013;21: 2163–71. 
  180. Hendricks EJ, Srisurapanont M, Schmidt SL, Haggard M, Souter S, Mitchell CL, et al. Addiction potential of phentermine prescribed during long-term treatment of obesity. Int J Obes (Lond) 2014;38:292–8. 
  181. Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. J Am Med Assoc 2016;315:2424–34. 
  182. Wyatt HR. Update on treatment strategies for obesity. J Clin Endocrinol Metab 2013;98:1299–306. 
  183. Domecq JP, Prutsky G, Leppin A, Sonbol MB, Altayar O, Undavalli C, et al. Clinical review: drugs commonly associated with weight change: a systematic review and meta-analysis. J Clin Endocrinol Metab 2015;100:363–70. 
  184. Graff SK, Mario FM, Ziegelmann P, Spritzer PM. Effects of orlistat vs. metformin on weight loss-related clinical variables in women with PCOS: systematic review and meta-analysis. Int J Clin Pract 2016;70:450–61. 
  185. Colquitt JL, Picot J, Loveman E, Clegg AJ. Surgery for obesity. Cochrane Database Syst Rev 2009:CD003641. 
  186. Colquitt JL, Pickett K, Loveman E, Frampton GK. Surgery for weight loss in adults. Cochrane Database Syst Rev 2014:CD003641. 
  187. Nudel J, Sanchez VM. Surgical management of obesity. Metabolism 2019; 92:206–16. 
  188. Adams TD, Pendleton RC, Strong MB, Kolotkin RL, Walker JM, Litwin SE, et al. Health outcomes of gastric bypass patients compared to nonsurgical, nonintervened severely obese. Obesity (Silver Spring) 2010;18: 121–30. 
  189. Wittgrove AC, Clark GW. Laparoscopic gastric bypass, Roux-en-Y- 500 patients: technique and results, with 3-60 month follow-up. Obes Surg 2000; 10:233–9. 
  190. CLevland clinic 
  191. Holst JJ, Madsbad S, Bojsen-Møller KN, Svane MS, Jørgensen NB, Dirksen C, et al. Mechanisms in bariatric surgery: gut hormones, diabetes resolution, and weight loss. Surg Obes Relat Dis 2018;14:708–14. 
  192. Kominiarek MA, Jungheim ES, Hoeger KM, Rogers AM, Kahan S, Kim JJ. American Society for Metabolic and Bariatric Surgery position statement on the impact of obesity and obesity treatment on fertility and fertility therapy endorsed by the American College of Obstetricians and Gynecologists and the Obesity Society. Surg Obes Relat Dis 2017;13:750–7. 
  193. Guelinckx I, Devlieger R, Vansant G. Reproductive outcome after bariatric surgery: a critical review. Hum Reprod Update 2009;15:189–201. 
  194. Maggard MA, Yermilov I, Li Z, Maglione M, Newberry S, Suttorp M, et al. Pregnancy and fertility following bariatric surgery: a systematic review. J Am Med Assoc 2008;300:2286–96. 
  195. Roos N, Neovius M, Cnattingius S, Trolle Lagerros Y, S€a€af M, Granath F, et al. Perinatal outcomes after bariatric surgery: nationwide population based matched cohort study. Br Med J 2013;347:f6460. 
  196. Johansson K, Cnattingius S, Naslund I, Roos N, Trolle Lagerros Y, Granath F, et al. Outcomes of pregnancy after bariatric surgery. N Engl J Med 2015; 372:814–24. 
  197. Stephansson O, Johansson K, N€aslund I, Neovius M. Bariatric surgery and preterm birth. N Engl J Med 2016;375:805–6. 
  198. Skubleny D, Switzer NJ, Gill RS, Dykstra M, Shi X, Sagle MA, et al. The impact of bariatric surgery on polycystic ovary syndrome: a systematic review and meta-analysis. Obes Surg 2016;26:169–76. 
  199. Tsur A, Orvieto R, Haas J, Kedem A, Machtinger R. Does bariatric surgery improve ovarian stimulation characteristics, oocyte yield, or embryo quality? J Ovarian Res 2014;7:116. 
  200. Milone M, De Placido G, Musella M, Sosa Fernandez LM, Sosa Fernandez LV, Campana G, et al. Incidence of successful pregnancy after weight loss interventions in infertile women: a systematic review and meta-analysis of the literature. Obes Surg 2016;26:443–51. 
  201. Tan O, Carr BR. The impact of bariatric surgery on obesity-related infertility and in vitro fertilization outcomes. Semin Reprod Med 2012;30: 517–28. 
  202. Beard JH, Bell RL, Duffy AJ. Reproductive considerations and pregnancy after bariatric surgery: current evidence and recommendations. Obes Surg 2008;18:1023–7. 
  203. Mechanick JI, Apovian C, Brethauer S, Garvey WT, Joffe AM, Kim J, et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures - 2019 update: cosponsored by American Association of Clinical Endocrinologists/ American College of Endocrinology, The Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists-executive summary. Endocr Pract 2019; 25:1346–59. 
  204. van Elten TM, Karsten MDA, Geelen A, Gemke RJBJ, Groen H, Hoek A, et al. Preconception lifestyle intervention reduces long term energy intake in women with obesity and infertility: a randomised controlled trial. Int J Behav Nutr Phys Act 2019;16:3. 
  205. van Oers AM, Mutsaerts MAQ, Burggraaff JM, Kuchenbecker WKH, Perquin DAM, Koks CAM, et al. Cost-effectiveness analysis of lifestyle intervention in obese infertile women. Hum Reprod 2017;32: 1418–26. 
  206. Kluge L, Bergh C, Einarsson S, Pinborg A, Mikkelsen Englund AL, Thurin-Kjellberg A. Cumulative live birth rates after weight reduction in obese women scheduled for IVF: follow-up of a randomized controlled trial. Hum Reprod Open 2019;2019:hoz030. 
  207. Mutsaerts MA. Randomized trial of a lifestyle program in obese infertile women. Ned Tijdschr Geneeskd 2016;160:D916. 
  208. Moran L, Tsagareli V, Norman R, Noakes M. Diet and IVF pilot study: short-term weight loss improves pregnancy rates in overweight/obese women undertaking IVF. Aust N Z J Obstet Gynaecol 2011;51:455–9. 
  209. Sim KA, Dezarnaulds GM, Denyer GS, Skilton MR, Caterson ID. Weight loss improves reproductive outcomes in obese women undergoing fertility treatment: a randomized controlled trial. Clin Obes 2014;4:61–8. 
  210. van Oers AM, Mutsaerts MAQ, Burggraaff JM, Kuchenbecker WKH, Perquin DAM, Koks CAM, et al. Association between periconceptional weight loss and maternal and neonatal outcomes in obese infertile women. PLoS One 2018;13:e0192670. 
  211. Espino's JJ, Sol'a I, Valli C, Polo A, Ziolkowska L, Martínez-Zapata MJ. The effect of lifestyle intervention on pregnancy and birth outcomes on obese infertile women: a systematic review and meta-analysis. Int J Fertil Steril 2020;14:1–9. 
  212. Dayan N, Spitzer K, Laskin CA. A focus on maternal health before assisted reproduction: results from a pilot survey of Canadian IVF medical directors. J Obstet Gynaecol Can 2015;37:648–55. 
  213. Kaye L, Sueldo C, Engmann L, Nulsen J, Benadiva C. Survey assessing obesity policies for assisted reproductive technology in the United States. Fertil Steril 2016;105:703–6.e2. 
  214. Romanski PA, Farland LV, Tsen LC, Ginsburg ES, Lewis EI. Effect of class III and class IV obesity on oocyte retrieval complications and outcomes. Fertil Steril 2019;111:294–301.e1. 
  215. NICE. Fertility problems: assessment and treatment. Clinical guideline [CG156]. In. Vol. 2020, 2013. 
  216. Legro RS. Effects of obesity treatment on female reproduction: results do not match expectations. Fertil Steril 2017;107:860–7. 
  217. Pandey S, Maheshwari A, Bhattacharya S. Should access to fertility treatment be determined by female body mass index? Hum Reprod 2010;25: 815–20. 
  218. Brown RCH. Irresponsibly infertile? Obesity, efficiency, and exclusion from treatment. Health Care Anal 2019;27:61–76. 
  219. Tremellen K, Wilkinson D, Savulescu J. Should obese women's access to assisted fertility treatment be limited? A scientific and ethical analysis. Aust N Z J Obstet Gynaecol 2017;57:569–74. 
  220. Gillett WR, Peek JC, Herbison GP. Development of clinical priority access criteria for assisted reproduction and its evaluation on 1386 infertile couples in New Zealand. Hum Reprod 2012;27: 131–41. 
  221. Kelley AS, Badon SE, Lanham MSM, Fisseha S, Moravek MB. Body mass index restrictions in fertility treatment: a national survey of OB/GYN subspecialists. J Assist Reprod Genet 2019;36:1117–25. 
  222. ACOG Committee Opinion No. 763: ethical considerations for the care of patients with obesity. Obstet Gynecol 2019;133:e90–6. 
  223. Sermondade N, Huberlant S, Bourhis-Lefebvre V, Arbo E, Gallot V, Colombani M, et al. Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis. Hum Reprod Update 2019;25:439–51. 
  224. Mahutte N, Kamga-Ngande C, Sharma A, Sylvestre C. Obesity and reproduction. J Obstet Gynaecol Can 2018;40:950–66. 
  225. Bellamy MC, Margarson MP. Designing intelligent anesthesia for a changing patient demographic: a consensus statement to provide guidance for specialist and non-specialist anesthetists written by members of and endorsed by the Society for Obesity and Bariatric Anaesthesia (SOBA). Perioper Med (Lond) 2013;2:12. 
  226. Joshi GP, Ahmad S, Riad W, Eckert S, Chung F. Selection of obese patients undergoing ambulatory surgery: a systematic review of the literature. Anesth Analg 2013;117:1082–91. 

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