Kathryn C. Calhoun1
(1)
Reproductive Endocrinology and Infertility, The Atlanta Center for Reproductive Medicine (ACRM), Atlanta, GA, USA
Kathryn C. Calhoun
Email: kcalhounmd@gmail.com
Abstract
Elevated body weight can decrease fertility in men and women. It increases the risk of ovulatory dysfunction and insulin resistance but can also decrease chance of conception in women with regular cycles. In men, excess adipose tissue can create an unfavorable endocrine profile and decrease sperm count and quality. Obstetrical morbidity and mortality, and metabolic consequences for the next generation, increase with elevated body weight so the ideal time to optimize BMI is preconception. Strategies for weight loss should center on caloric restriction and increased physical activity, but can utilize medication and surgery as adjuncts.
Keywords
ObesityInfertilityAnovulationPCOSInsulin resistanceGlucose intoleranceBody mass index (BMI)
Aside from tobacco use, obesity is the most modifiable risk factor for infertility.
Key Points
· Existing evidence suggests that elevated body weight has a detrimental effect on both male and female fertility.
· Elevated body weight exacerbates Polycystic Ovary Syndrome [1] and reduces the chance of ovulation, in both medicated and unmedicated cycles.
· Elevated body weight reduces the chance of pregnancy and live birth, in both medicated and unmedicated cycles.
· Weight loss appears to improve health, fertility, and life expectancy.
· All weight loss and weight maintenance strategies should include both diet and exercise.
Definitions
· Infertility: No conception despite 1 year of unprotected intercourse
· Body mass index (BMI): A standardized expression of body size, as determined by weight in kilograms divided by height in meters squared (kg/m2):
· <19: Underweight
· 19–24.9: Normal BMI
· 25–29.9: Overweight
· 30–34.5: Obesity I
· 35–39.9: Obesity II
· ≥40: Obesity III
· Ovulatory dysfunction: The failure to predictably release an oocyte in a cyclic fashion (also known as “oligo-ovulation” or “anovulation”)
· Insulin: Hormonal regulator of the body’s use of glucose (sugar) and fat; produced by the pancreas
· Insulin resistance: Failure of the body’s cells to take up glucose from the blood in response to “normal” amounts of blood insulin
· Glucose intolerance: As a result of insulin resistance (and/or inadequate insulin production by the pancreas), blood glucose levels are chronically elevated
· “Prediabetes”: May refer to insulin resistance +/− glucose intolerance
· Resting metabolic rate (RMR): The number of calories consumed daily for bodily homeostasis
The Scope of the Problem
Infertility, defined as no conception after 1 year of unprotected intercourse, affects 15 % of the US population or over seven million couples [2]. In the USA, roughly 1 % of children are conceived via in vitro fertilization (IVF), with many more couples employing less aggressive medical assistance (i.e., ovulation induction medicines, intrauterine insemination) [2].
A devastating and related problem is the pandemic of obesity. Worldwide, more people are obese than starving [3]. In the USA, over 60 % of adults are above their ideal body weight; approximately 36 % of adults and 17 % of children and adolescents (<19 years old) are obese [2]. There are racial discrepancies in obesity, with 50 % of African Americans struggling with obesity. Individuals with elevated body weight suffer more illness (cardiovascular, psychological, oncologic) and earlier deaths than their counterparts who maintain an ideal body weight (CDC) [2, 4, 5]. Women who are overweight and obese have additional consequences of obstetrical and gynecologic morbidities, and both sexes have reduced fertility at elevated body weights [6, 7]. Aside from tobacco use, obesity is the most modifiable risk factor for morbidity, mortality, and infertility.
Obesity and Female Fertility
Although one large study found no significant difference in fecundity between BMI groups, the majority of the literature suggests that fecundity declines with increasing BMI [7, 8]. Decreased fertility in the obese population relates primarily to ovulatory dysfunction (“anovulation” or “oligo-ovulation”), or the failure to reliably release a mature oocyte in a cyclic fashion. In fact, BMI at age 18 has been shown to predict the risk of anovulatory infertility and nulliparity [9]. Approximately 30–47 % of overweight women have menstrual irregularities [1]. Weight loss, even modest amounts of 5–10 % of body weight, has been shown to increase the likelihood of ovulation and conception, in both medically unassisted and assisted cycles [8, 10].
There is evidence that ovulatory disorders may not be the only explanation for decreased fecundity in heavier women. Even in ovulatory women, time to conception (TTC) is more likely to be greater than 6 months in women with elevated body weight. Even after controlling for menstrual regularity, women with more visceral adiposity had a longer time to conception [11]. One study of over 3,000 ovulatory women with at least one normal tube and access to normal sperm demonstrated that pregnancy rate (PR) declined 4 % per year for every BMI unit over 29 [12]. Other factors may be involved, such as the uterus, the gamete quality, the endocrine milieu, or the presence of chronic inflammation.
Anovulation
The hypothalamic-pituitary-gonadal axis is quite vulnerable to the effects of stress, illness, and weight changes, likely reflecting an evolutionary adaptation designed to prevent increases in the population during times of starvation, conflict, or disease.
In the beginning of an ovulatory cycle, the pituitary gland responds to hypothalamic GnRH pulses with release of follicle-stimulating hormone (FSH), aimed at developing the cohort of follicles that have been recruited in the luteal phase of the previous cycle. As early as cycle day 5, a dominant follicle emerges, with superior blood flow and FSH-receptor concentrations, able to survive even when FSH secretion is attenuated in response to rising ovarian estrogen and inhibin B levels [13]. When estrogen concentrations are sustained at a threshold level (200 pg/ml) for approximately 50 h (reflecting a mature oocyte), central estrogen feedback then becomes stimulatory and pituitary luteinizing hormone (LH) is released to affect final maturation of the mature egg/follicle and, ultimately, ovulation.
There are many points in the ovulatory menstrual cycle that can be disrupted by elevated body weight/adiposity. Adipose tissue possesses aromatase and is, therefore, capable of converting peripheral androgens to estrogens (estrone). This chronic elevation of estrogen may prevent the late luteal FSH rise that is necessary to recruit a cohort of follicles for the subsequent cycle. In addition, the hypothalamic GnRH pulsatility can be altered, thereby preventing the proper ratios of FSH/LH secretion to produce a dominant follicle. Without proper stimulation and feedback loops between the brain and the ovary, the entire cohort remains immature and is not able to sustain the necessary estrogen level/duration that is necessary to trigger the LH surge for ovulation. To compound the dysfunction, the risk of insulin resistance/hyperinsulinemia increases with excess body weight [14]. Insulin stimulates ovarian androgen production directly, but also indirectly by increasing LH secretion. Insulin also decreases hepatic production of sex hormone-binding globulin, with a net effect of increased circulating free androgens. Free androgens impair proper follicular development and can have undesired peripheral effects such as increased acne and impaired hair growth (both hirsutism and male patterned baldness). The situation further compounds itself because immature eggs/follicles eventually become atretic and join the stromal tissue of the ovary, where they begin to produce ovarian androgens and worsen the problem. Chronic elevation of LH and also leptin, a protein hormone which regulates satiety, can impair granulosa cells, and thus follicular, function [15, 16]. Insulin resistance and hyperandrogenism are arguably the central driving forces in the pathophysiology of Polycystic Ovary Syndrome (PCOS).
Polycystic Ovary Syndrome
PCOS, according to the original 1990 NIH criteria, represents a subset of anovulatory women who also suffer from hyperandrogenism [16]. The diagnosis can be made based on menstrual history and clinical or laboratory evidence of elevated androgens, after excluding other possible disorders (i.e., nonclassical congenital adrenal hyperplasia, hyperprolactinemia, hypercortisolism, thyroid dysfunction) [16]. Because these women suffer prolonged periods of anovulation, their ovaries become enlarged with excess stromal (thecal) mass from months of follicular atresia. Amongst the excess stroma, many immature follicles remain, giving the ovaries in this syndrome their “polycystic” appearance on ultrasound. As discussed above, theca cells in the increased stroma produce androgens in response to LH, and they seem to be more sensitive to LH in the ovaries of women with PCOS [14]. Though obesity is not a criterion for PCOS, adiposity contributes to anovulation, insulin resistance, and, therefore, hyperandrogenism, and a substantial majority of women with PCOS also struggle with their weight. Estimates suggest 30–80 % of women with PCOS are obese, depending on ethnicity [16]. Lean women with PCOS have more fat than non-PCOS women, matched for BMI, but they seem to have lesser degrees of hyperinsulinemia and hyperandrogenism and metabolic disturbance [14, 16]. Hyperandrogenism has been implicated in aggravation of visceral adiposity and insulin resistance [17, 18]. Hyperinsulinemia aggravates hyperandrogenism; the conditions propagate each other and the PCOS.
Significance
The importance of distinguishing women with PCOS from other women with anovulation is that PCOS women suffer greater metabolic consequences, owing to their concomitant insulin and androgen disruptions. In contrast to 1990 NIH criteria, the 2004 Rotterdam ESHRE PCOS definition requires manifestation of any two of the following three criteria: ovulatory dysfunction, hyperandrogenism, and/or polycystic ovaries on ultrasound [1]. Thus, Rotterdam criteria PCOS does not require hyperandrogenism. However, women without hyperandrogenism do not seem to manifest the same metabolic perturbations, prompting the Androgen Excess Society to reaffirm the necessity of hyperandrogenism and anovulation for inclusion in PCOS [19, 20].
Management
Due to the increased risk of metabolic consequences, women with PCOS should be screened annually with a fasting lipid panel (for hypercholesterolemia) and a 75-g, 2-h glucose tolerance test (for insulin resistance and glucose intolerance). Obese women with PCOS have 7–10 times the risk of developing insulin/glucose abnormalities as normal subjects [16]. Clearly, diet and exercise are essential to controlling cholesterol and insulin sensitivity and to combatting weight gain which increases the metabolic risks. Abdominal obesity and weight gain in the teenage years are risk factors for developing PCOS [21]. Many features of PCOS resolve following weight loss with bariatric surgery [22, 23].
In addition to diet and exercise directed at achieving and maintaining a healthy weight, therapy for women with PCOS must address their ovulatory dysfunction and hyperandrogenism. For women who are not trying to conceive, cycle regulation is best accomplished with a combined oral contraceptive pill (cOCP). In addition to cycle regulation, the estrogen in combined hormonal preparations stimulates hepatic SHBG production to decrease free androgens. For women who wish or need to avoid estrogen, progesterone-only options include cyclic progesterone administrations (not contraceptive), Implanon® (Merck Pharmaceuticals), Depo-Provera® (Pfizer), or a Mirena® (Bayer Healthcare) IUD. It is imperative that all anovulatory women avoid chronic unopposed endometrial estrogen exposure, which can lead to endometrial cancer. Progesterone-only methods prevent unopposed estrogen exposure, provide some cycle regulation, and can decrease LH-driven ovarian androgen production.
Hyperandrogenism is treated with cosmetic removal of existing hair growth and prevention of further hair follicle virilization with antiandrogen medications. As discussed above, estrogen-containing cOCPs increase SHBG to decrease free androgens. All hormonal contraceptives may decrease ovarian androgen production. Antiandrogen medications include spironolactone (a diuretic with actions against the androgen receptor) and inhibitors of 5-alpha reductase (blocks peripheral conversion of weak androgens to the more potent DHT). Antiandrogen medicines must be used in conjunction with contraception, due to their potential teratogenicity in male fetuses. Antiandrogens and cOCPs are, unfortunately, less efficacious in obese women, providing more reason to optimize weight in the treatment of PCOS [24, 25].
For women trying to conceive, anovulation is treated with oral (i.e., clomiphene citrate, letrozole) or injectable (FSH, LH) ovulation induction agents. As discussed above, antiandrogen medications are contraindicated in the periconception or pregnancy period.
The insulin-sensitizing agent, Metformin, is discussed below. It has been considered as an adjunct to ovulation induction strategies in women with PCOS, especially in women with demonstrated insulin or glucose abnormalities. Recent studies have suggested that some women with PCOS and insulin resistance have defects and/or deficiencies inositolphosphoglycan (IPG) mediators of insulin action. Myo-inositol (Pregnitude) is a supplement that has demonstrated improvements in insulin levels, cutaneous symptoms (acne, hair), and ovulation induction [26, 27].
Obesity and Male Fertility
There is concordance between partners for weight and BMI, amongst other cardiovascular risk factors [28, 29]. This finding may be due to assortative mating and/or shared environment, and two partners with excess adiposity can potentiate problems with sexuality and fertility. It is essential that research on weight/BMI and fertility include parameters for both partners.
Though frequency of sexual activity is similar in obese versus nonobese females, positional difficulties may affect frequency of intercourse in very obese women. Notably, orgasm and sexual satisfaction are negatively correlated with BMI in women and impotence and erectile dysfunction are increased in overweight and obese men [30]. Some of these effects may also be due to comorbidities, such as diabetes mellitus and depression [2].
Men with excess body weight often suffer impaired spermatogenesis. Three clinical studies have shown that obesity, as indicated by body mass index, is associated with decreased sperm concentration and motility [31–33]. Two of these studies involved males presenting with their partners for infertility treatment, and one was a study of young adult volunteers without an infertility diagnosis presenting for a routine medical examination. Significant correlations between reproductive hormone levels and BMI were observed in the study of normal volunteers [31]. From a hypothalamic-pituitary-gonadal standpoint, higher estrogen levels from adipose aromatization suppresses the LH and FSH drives to stimulate testicular testosterone and sperm production, respectively. Levels of sex hormone-binding globulin are often lowered by the estrogen so these men may demonstrate elevated free androgen levels, though testicular testosterone is suppressed, impairing spermatogenesis and, possibly, sexuality [31, 33].
At a local level, there may also be a deleterious impact from increased amounts of suprapubic and thigh fat, possibly from elevated scrotal temperatures. Improved semen quality and pregnancy rates have been reported after scrotal/suprapubic lipectomy, though this is not routinely employed [34, 35].
Similar to women, weight loss appears to benefit male fertility, with improvements in semen parameters. A 2009 study examined the relationship between BMI and reproductive hormones in obese men undergoing Roux-en-Y gastric bypass surgery and discovered that BMI correlated positively with estradiol and negatively with testosterone. Further, estradiol decreased and testosterone increased with significant postoperative weight loss. Sexual quality of life was also improved with weight loss [35]. Though one case series from Italy reported six patients who presented with secondary infertility due to nonobstructive azoospermia following Roux-en-Y gastric bypass surgery, other research studies suggest that obesity is associated with diminished sperm function and that weight loss might improve fertility [35, 36].
Infertility Treatment for the Obese Female Patient
Infertility treatment is more successful for women who are closer to their ideal body weight. For anovulatory patients, rates of both ovulation and conception with the oral ovulation induction agent clomiphene citrate are higher at lower BMIs [8]. After ovulation induction is successful, live birth rates are higher for nonobese women [8].
During in vitro fertilization (IVF) cycles, women who have elevated body weights require more medications for a longer duration and still suffer more cancellations, fewer eggs retrieved, fewer embryos transferred, lower pregnancy rates, and more miscarriages [37].
The obstetrical morbidities associated with elevated body weight are discussed elsewhere in this book but include higher rates of miscarriage, birth defects, gestational diabetes, preeclampsia, cesarean section, and still birth [37–39]. These increased risks hold true for overweight and obese women after conception with IVF [40].
Both the American Congress of Obstetricians and Gynecologists [41] and the American Society for Reproductive Medicine [1] advocate for achieving a healthy weight/BMI prior to conception [1, 41]. Advocates of the Barker hypothesis stress the impact of the in-utero environment on long-term health status and outcomes, and the lifetime consequences of obesity during pregnancy which include metabolic sequelae, that predispose the next generation to obesity and diabetes [42].
Though “normal” BMI is established as 19.5–24.9, there is no current consensus on a BMI cutoff for conception. Many independent clinics have established cutoffs for fertility treatment but, with weight problems being nearly ubiquitous, many practitioners encounter the ethical dilemma of delaying fertility treatment in a woman with dwindling ovarian reserve. As obesity and advanced maternal age may compound the risk for the same obstetrical morbidities, it seems counterintuitive to advocate pursuit of conception prior to weight loss in these women, but it may be construed as cruel to deny them an opportunity to conceive with their own oocytes.
Achieving a “normal” weight/BMI is a clear component of optimizing preconception health and should be included in any preconceptual counseling. Some women are very obese and may not ever achieve a BMI <25; in those populations, some have advocated that a BMI <35 be the target [1].
Strategies for Weight Loss
The formula for weight loss is simple: consume fewer calories than are needed to support daily activity. Operationalizing this strategy is difficult, as daily attention to caloric restriction and increased activity represents a huge life change for many individuals. Though tedious and initially awkward, it can (and must!) be done – without implementation of regular exercise, the basal metabolic rate declines with age (~2 %/decade over age 18) (acefitness.org). Everyone must incorporate diet and exercise to maintain a healthy weight; individuals who are overweight must initially restrict more aggressively to lose excess weight.
Diet
To a degree, the exact composition of the diet does not seem to be as important as the overall caloric restriction. Studies have shown low-carbohydrate and low-fat diets to achieve equivalent weight loss at 1 year and equivalent decreases in insulin, CRP, and cholesterol. One exception to this statement may be women with PCOS or individuals with insulin resistance, glucose intolerance, or “prediabetes” – in this case, a diet that pays attention to the glycemic index can be useful. The glycemic index is an objective way to measure a food’s effect on blood sugar; foods with higher glycemic index scores raise blood sugar more abruptly, creating “spikes” and subsequent “crashes.” Both ends of the spectrum can be unpleasant and may make a diet harder to follow. Complex carbohydrates and proteins have a lower glycemic index (under 55) meaning that they have a slower, steadier effect on blood glucose and insulin levels [43]. Low glycemic index translates into fewer blood glucose peaks and valleys, fewer surges in insulin demands, and fewer “shaky” episodes where the dieter may run to the closest vending machine for a quick glucose fix.
Sadly, most diets fail. The average weight regained by dieters is 60–85 % at 3 years and 75–120 % by 5 years [1]. The reason for this failure is that most diets are short-term plans and are not sustainable lifestyle changes. As discussed above, aging brings a predictable decrease in basal metabolic rate, making progressive caloric restriction and regular exercise vital to maintaining a healthy weight. It is essential for the individual dieter to embrace a long-term plan; extreme restriction is typically not sustainable.
A healthy rate of weight loss should not exceed 1–2 lb/week. One method to calculate daily caloric intake is to compute the resting metabolic rate (RMR) or the number of calories required to keep the body’s basic functions running on a daily basis; RMR does not take into account additional exercise. Subtracting 500 cal from RMR will give an approximate daily caloric limit for losing 1–2 lb/week.
Resources permitting, it is helpful for the dieter to seek help from a nutritionist or endocrinologist. These professionals can help to design meal plans and calorie counts that take into account the individual dieter’s goals, food preferences/cravings, and past experiences. Studies show that dieters in organized programs fare better [44].
Exercise
Physical activity has many benefits; not only does it reliably improve cardiovascular health but it is an essential adjunct to diet for individuals pursuing weight loss (AHA). Exercise builds upon the RMR to burn more calories and assist in weight loss. Additionally, exercise has proven effects on improving insulin sensitivity and thus glucose utilization [14]. Improvements in insulin sensitivity may well improve chances for ovulation.
The American Heart Association (AHA) recommends moderate activity for 150 min/week or vigorous activity for 75 min/week. ACOG echoes the merits of moderate exercise, even for women with uncomplicated pregnancies, recommending 30–45 min on most, if not all, days [41]. There is mounting evidence that interval training, incorporating bursts of increased exertion upon a longer period of moderate exertion, may be superior to moderate activity in improving both fitness and cardiovascular profiles [45].
As with dieting, there is an advantage to seeking out professional advice from a trainer or a staff member at a local gym/fitness center. At the very least, exercising with another person may improve compliance.
Medications
There are pharmaceutical preparations available for individuals who do not achieve adequate weight loss after 6 months of diet and exercise. Medical interventions may be reserved for those with a BMI ≥30 or ≥27 with comorbidities. On average, users demonstrate loss of an additional 2–4 kg over 7–48 weeks, representing a broad spectrum of results [46]. It must be stressed that adjunctive treatments, including medicines, must be combined with diet and regular exercise.
Sympathomimetics, i.e., Phentermine (Adipex) or Diethylpropion (Anorex, Tenuate)
These are norepinephrine stimulant and reuptake inhibitors that function as appetite suppressants. They are to be used with caution in cardiovascular disease patients and pregnancy (Class C). Patients should have regular blood pressure and weight checks. Studies have shown loss of an additional 3.6 kg/6 months vs. placebo [46].
Anti-absorptives, i.e., Orlistat (Xenical, Alli)
These are a derivative of natural inhibitor of pancreatic lipases shown to block intestinal fat absorption by 30 %. As a result, they also block the fat-soluble vitamins (ADEK). These should not be used for malabsorption or cholestasis patients. Gastrointestinal (GI) side effects, though rare, can affect the liver and kidney. Studies have shown loss of an additional 2.9 kg/12 months vs. placebo and, possibly, improved lipids and Hemoglobin A1C levels [46].
Insulin Sensitizers (Metformin/Glucophage)
This is a biguanide that inhibits hepatic glucose production and increases peripheral tissue insulin sensitivity. It often has GI side effects (diarrhea), though newer extended release preparations seem to be better tolerated. Studies have shown loss of an additional 1–2 kg more than placebo so this should not be used primarily as a weight-loss drug but more as an adjunct to exercise for patients with insulin resistance [47].
Myo-inositol (Pregnitude)
As discussed above, this medication may mediate insulin actions, thereby reducing serum insulin and testosterone levels, treating cutaneous disorders associated with hyperandrogenism (hair, acne) and enhancing ovulation [26, 27]. Though Metformin is currently the first-line medication for PCOS patients with insulin resistance, Myo-inositol appears to be a useful alternative, particularly for patients who cannot tolerate Metformin.
Androgen-Reducing Medications
As discussed above, these may be a critical adjunct to improving insulin sensitivity in women with hyperandrogenism. Spironolactone is a diuretic with antagonistic effects on the androgen receptor. Inhibitors of 5-alpha reductase block the conversion of weak androgens to the more potent DHT, which mediates all virilizing effects on hair follicles and sebaceous units. As discussed, these must be used with contraception.
Antidepressants (SSRIs), Antiepileptics
These categories of medications have demonstrated weight loss for some patients in trials for their primary indications. However, some patients have demonstrated weight gain while on these medicines so they should not be prescribed for weight loss [1].
Ephedra/Ephedrine (Ma Huang)
Sold as an herbal supplement over the counter, this compound is a sympathomimetic that results in increased thermogenesis and acts as an appetite suppressant. Studies have shown loss of only an additional 0.6–1 kg weight per month, when compared to placebo, and this compound carries several side effect risks, including cardiovascular, GI, central nervous system, and psychiatric. It is, therefore, not recommended for weight loss [48].
Surgery
Bariatric (weight loss) surgery, first introduced in the 1960s, is recognized as the most effective treatment for Class 3 obesity [49]. It is typically reserved for patients with a BMI ≥40 or ≥35 with comorbidities, who have failed other interventions. Preoperative treatment includes intensive screening and demonstrating ability to comply with aggressive caloric restriction. There are two general categories of bariatric surgery: restrictive and malabsorptive. The former includes banding procedures and is a reversible way of decreasing the size of the stomach and increasing satiety. The latter is often a permanent anatomic alteration that results in a smaller stomach and, often, a marked reduction in absorptive intestinal surface. Both types of surgery produce dramatic weight loss postoperatively, though the malabsorptive procedures seem to result in greater total weight loss, longer sustained weight loss, and also, more nutritional deficits and considerations.
The goal of bariatric surgery is to improve obesity and related conditions. The mortality rate is less than 1 %, and it does seem to improve high blood pressure, diabetes, cholesterol, and sleep apnea. As mentioned above, the balance of evidence seems to support its role in improving both male and female fertility, including the manifestations of PCOS [1]. Eighty percent of bariatric surgery patients are female and, as the obstetrical and gynecologic community cares for more women after surgery, guidelines have been generated. Currently, it is recommended to defer pregnancy for 1 year postoperatively, as the majority of weight loss occurs during this time frame. Careful attention must be paid to iron, folate, B12, calcium, and the fat-soluble vitamins (ADEK) [49, 50]. Limited data from observational studies suggest that, after surgery-induced weight reduction, women enjoy a reduction of gestational diabetes mellitus and gestational hypertensive disorders when compared to their obese counterparts. Further research is needed on macrosomia, growth restriction, and preterm birth [50].
Future Directions
Elevated body weight affects the health, longevity, and fertility of both men and women. The burgeoning obesity pandemic threatens to shorten the life expectancy and fecundity of our species. In addition to ongoing research on the exact pathophysiology underlying obesity and its comorbid conditions, future efforts should focus on patient education and preventative health measures directed at achieving healthier body weights.
Leading medical organizations have instructed providers to assess patient weight and triage overweight and obese patients to treatment [51]. Studies have shown that patients who receive advice to lose weight are nearly three times more likely to report trying to lose weight than those who do not, thus underscoring the role of the healthcare provider as the impetus for change [52]. Unfortunately, less than half of obese adults in the USA report weight loss counseling by their care provider [52]. A recent survey found that women’s healthcare providers neglect to counsel overweight and obese patients, even when they correctly recognize them as overweight/obese and acknowledge that they need counseling. The leading barrier to counseling was time constraints during the visit [53].
The United States Preventative Services Task Force concluded that physician counseling alone was only modestly effective but results could be improved by adding weight loss education and support [51]. Therefore, physicians and healthcare providers must identify women who are overweight and triage them to specialists in diet, exercise, psychological counseling, and bariatric surgery. Cultivating a lattice of physician extenders to help with weight loss will alleviate time pressures on the primary provider and improve the specialized quality of treatment and counseling. The critical step in this process is that the primary provider must communicate to the patient that they are overweight, identify weight loss as a priority, and provide the referral to an expert in weight reduction. If the primary provider abdicates this responsibility (and simply treats the sequelae of unchecked weight gain), the obesity epidemic will continue to claim the health and longevity of our friends and family.
It is quite possible that we need a paradigm shift towards treating obesity as an addiction, akin to other eating disorders. Intensive therapy and/or inpatient programs are likely necessary for severe and refractory cases of obesity. In addition, financial incentives have been shown to maintain weight loss group attendance so it may be helpful to institute token economies via insurance premium discounts for healthy behaviors [54–56].
Healthcare practitioners who see reproductive-aged women are the gatekeepers of maternal-fetal health. They must recognize and discuss the effects of excess body weight on reproduction and obstetrical morbidity and facilitate weight loss before pregnancy to prevent perpetuation of the obesity epidemic and its threat to fertility, wellness, and longevity.
References
1.
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41–7.
2.
Centers for Disease Control and Prevention. Where are United States ART clinics located, how many ART cycles did they perform in 2009, and how many infants were born from these ART cycles? http://www.cdc.gov/art/ART2009/section1.html. Accessed on 22 Sep 2013.
3.
International Red Cross. Obesity in the Background of Malnutrition. http://www.ifrc.org/. Accessed on 22 Sep 2013.
4.
Manson JE, et al. Body weight and mortality among women. N Engl J Med. 1995;333(11):677–85.PubMed
5.
Williamson DF, et al. Prospective study of intentional weight loss and mortality in never-smoking overweight US white women aged 40–64 years. Am J Epidemiol. 1995;141(12):1128–41.PubMed
6.
Watkins ML, et al. Maternal obesity and risk for birth defects. Pediatrics. 2003;111(5 Pt 2):1152–8.PubMed
7.
Howe G, et al. Effects of age, cigarette smoking, and other factors on fertility: findings in a large prospective study. Br Med J (Clin Res Ed). 1985;290(6483):1697–700.
8.
Legro RS, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007;356(6):551–66.PubMed
9.
Rich-Edwards JW, et al. Adolescent body mass index and infertility caused by ovulatory disorder. Am J Obstet Gynecol. 1994;171(1):171–7.PubMed
10.
Clark AM, et al. Weight loss results in significant improvement in pregnancy and ovulation rates in anovulatory obese women. Hum Reprod. 1995;10(10):2705–12.PubMed
11.
Zaadstra BM, et al. Fat and female fecundity: prospective study of effect of body fat distribution on conception rates. BMJ. 1993;306(6876):484–7.PubMed
12.
van der Steeg JW, et al. Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. Hum Reprod. 2008;23(2):324–8.PubMed
13.
Chikazawa K, Araki S, Tamada T. Morphological and endocrinological studies on follicular development during the human menstrual cycle. J Clin Endocrinol Metab. 1986;62(2):305–13.PubMed
14.
Legro RS. Obesity and PCOS: implications for diagnosis and treatment. Semin Reprod Med. 2012;30(6):496–506.PubMed
15.
Jungheim ES, Moley KH. Current knowledge of obesity’s effects in the pre- and periconceptional periods and avenues for future research. Am J Obstet Gynecol. 2010;203(6):525–30.PubMed
16.
Vrbikova J, Hainer V. Obesity and polycystic ovary syndrome. Obes Facts. 2009;2(1):26–35.PubMed
17.
Elbers JM, et al. Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects. Clin Endocrinol (Oxf). 2003;58(5):562–71.
18.
Dahlgren E, et al. Effects of two antiandrogen treatments on hirsutism and insulin sensitivity in women with polycystic ovary syndrome. Hum Reprod. 1998;13(10):2706–11.PubMed
19.
Barber TM, et al. Metabolic characteristics of women with polycystic ovaries and oligo-amenorrhoea but normal androgen levels: implications for the management of polycystic ovary syndrome. Clin Endocrinol (Oxf). 2007;66(4):513–7.
20.
Azziz R, et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab. 2006;91(11):4237–45.PubMed
21.
Laitinen J, et al. Body size from birth to adulthood as a predictor of self-reported polycystic ovary syndrome symptoms. Int J Obes Relat Metab Disord. 2003;27(6):710–5.PubMed
22.
Escobar-Morreale HF, et al. The polycystic ovary syndrome associated with morbid obesity may resolve after weight loss induced by bariatric surgery. J Clin Endocrinol Metab. 2005;90(12):6364–9.PubMed
23.
Hezelgrave NL, Oteng-Ntim E. Pregnancy after bariatric surgery: a review. J Obes. 2011;2011:501939.PubMed
24.
Koulouri O, Conway GS. A systematic review of commonly used medical treatments for hirsutism in women. Clin Endocrinol (Oxf). 2008;68(5):800–5.
25.
Cibula D, Hill M, Fanta M, Sindelka G, Zivny J. Does obesity diminish the positive effect of oral contraceptive treatment on hyperandrogenism in women with polycystic ovary syndrome? Hum Reprod. 2001;16:940–4.PubMed
26.
Zacche MM, et al. Efficacy of myo-inositol in the treatment of cutaneous disorders in young women with polycystic ovary syndrome. Gynecol Endocrinol. 2009;25(8):508–13.PubMed
27.
Papaleo E, et al. Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction. Gynecol Endocrinol. 2007;23(12):700–3.PubMed
28.
Speakman JR, et al. Assortative mating for obesity. Am J Clin Nutr. 2007;86(2):316–23.PubMed
29.
Di Castelnuovo A, Quacquaruccio G, Donati MB, de Gaetano G, Iacoviello L. Spousal concordance for major coronary risk factors: a systematic review and meta-analysis. Am J Epidemiol. 2009;169(1):1–8.PubMed
30.
Yaylali GF, Tekekoglu S, Akin F. Sexual dysfunction in obese and overweight women. Int J Impot Res. 2010;22(4):220–6.PubMed
31.
Jensen TK, et al. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril. 2004;82(4):863–70.PubMed
32.
Koloszar S, et al. Effect of body weight on sperm concentration in normozoospermic males. Arch Androl. 2005;51(4):299–304.PubMed
33.
Kort HI, et al. Impact of body mass index values on sperm quantity and quality. J Androl. 2006;27(3):450–2.PubMed
34.
Shafik A, Olfat S. Lipectomy in the treatment of scrotal lipomatosis. Br J Urol. 1981;53(1):55–61.PubMed
35.
Hammoud A, et al. Effect of Roux-en-Y gastric bypass surgery on the sex steroids and quality of life in obese men. J Clin Endocrinol Metab. 2009;94(4):1329–32.PubMed
36.
di Frega AS, et al. Secondary male factor infertility after Roux-en-Y gastric bypass for morbid obesity: case report. Hum Reprod. 2005;20(4):997–8.PubMed
37.
Fedorcsak P, et al. Impact of overweight and underweight on assisted reproduction treatment. Hum Reprod. 2004;19(11):2523–8.PubMed
38.
Wang JX, Davies M, Norman RJ. Body mass and probability of pregnancy during assisted reproduction treatment: retrospective study. BMJ. 2000;321(7272):1320–1.PubMed
39.
Marshall NE, Spong CY. Obesity, pregnancy complications, and birth outcomes. Semin Reprod Med. 2012;30(6):465–71.PubMed
40.
Dokras A, et al. Obstetric outcomes after in vitro fertilization in obese and morbidly obese women. Obstet Gynecol. 2006;108(1):61–9.PubMed
41.
ACOG Committee Obstetric Practice. ACOG Committee opinion. Number 267, January 2002 exercise during pregnancy and the postpartum period. Obstet Gynecol. 2002;99(1):171–3.
42.
Frias AE, Grove KL. Obesity: a transgenerational problem linked to nutrition during pregnancy. Semin Reprod Med. 2012;30(6):472–8.PubMed
43.
Foster-Powell K, Holt SH, Brand-Miller JC. International table of glycemic index and glycemic load values: 2002. Am J Clin Nutr. 2002;76(1):5–56.PubMed
44.
Wadden TA, Foster GD. Behavioral treatment of obesity. Med Clin North Am. 2000;84(2):441–61. vii.PubMed
45.
Kessler HS, Sisson SB, Short KR. The potential for high-intensity interval training to reduce cardiometabolic disease risk. Sports Med. 2012;42(6):489–509.PubMed
46.
Li Z, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med. 2005;142(7):532–46.PubMed
47.
Fontbonne A, et al. The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO Study Group. Diabetes Care. 1996;19(9):920–6.PubMed
48.
Shekelle P, et al. Ephedra and ephedrine for weight loss and athletic performance enhancement: clinical efficacy and side effects. Evid Rep Technol Assess (Summ). 2003;(76):1–4.
49.
American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 105: bariatric surgery and pregnancy. Obstet Gynecol. 2009;113(6):1405–13.
50.
Hezelgrave NL, Oteng-Ntim E. Pregnancy after bariatric surgery: a review. J Obes. 2011;2011:1–5.
51.
McTigue KM, et al. Screening and interventions for obesity in adults: summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2003;139(11):933–49.PubMed
52.
Galuska DA, et al. Are health care professionals advising obese patients to lose weight? JAMA. 1999;282(16):1576–8.PubMed
53.
Evans-Hoeker E, Calhoun KC, Mersereau JE. Healthcare provider accuracy at estimating Women’s BMI and intent to provide counseling based on appearance alone. Obesity (Expected publication, Dec 2013).
54.
Sperduto WA, O’Brien RM. Effects of cash deposits on attendance and weight loss in a large-scale clinical program for obesity. Psychol Rep. 1983;52(1):261–2.PubMed
55.
Petry NM, et al. A low-cost reinforcement procedure improves short-term weight loss outcomes. Am J Med. 2011;124(11):1082–5.PubMed
56.
Volpp KG, et al. Financial incentive-based approaches for weight loss: a randomized trial. JAMA. 2008;300(22):2631–7.PubMed