There is a mounting body of evidence suggesting that maternal obesity may confer a risk of metabolic dysfunction through multiple generations.

Children of obese mothers are more likely to develop obesity, type 2 diabetes, and cardiovascular disease as adults.

It is complex and multifactorial. Several mechanisms are involved in the relationship between fertility and obesity.

Adipokines are the signalling molecules (hormones) secreted by adipose tissue, and abnormalities in adipokines can cause inflammation and abnormal cell signalling, and thus can lead to deterioration in cell metabolism and function.

Some of these adipokines are leptin, adiponectin, interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), tumour necrosis factor-α (TNF-α), resistin, visfatin, chemerin, omentin, and ghrelin.

High levels of leptin seen in obesity may inhibit folliculogenesis. High levels of leptin interfere with endometrial receptivity and embryo implantation. Leptin levels have been found to be positively correlated with insulin resistance in women with polycystic ovarian syndrome (PCOS).

Adiponectin levels increase with weight loss. In the absence of adiponectin in obese women, plasma insulin levels increase. Consequently, high levels of insulin lead to hyperandrogenaemia.

IL-6, in the high levels seen in obese women, may contribute to impaired fertility in women with PCOS.

PAI-1 has been associated with miscarriage in women with PCOS.

TNF-α may affect several levels of the reproductive axis: inhibition of gonadotrophin secretion, ovulation, steroidogenesis, corpus luteum regression, and endometrial development.

The mechanism of other adipokines on reproductive functions such as resistin and ghrelin has not been fully understood.

Increased resistin levels seen in obesity leads to insulin resistance and leads to decreased insulin sensitivity.

Visfatin, shows insulin-mimetic effects, that increases glucose uptake in adipocytes and muscle cells, and decreases glucose release from hepatocytes.

Chemerin can impair follicle-stimulating hormone (FSH)-induced follicular steroidogenesis and thus can play a role in the pathogenesis of PCOS.

Almost all of the adipokines seem to have their effects on reproduction by causing insulin resistance ( Table 7.1 ).

Obesity has a negative effect on reproductive potential, primarily thought to be due to functional alteration of the HPO axis.

Obese women often have higher circulating levels of insulin, which is a known stimulus for increased ovarian androgen production. These androgens are aromatised to oestrogen at high rates in the periphery owing to excess adipose tissue, leading to negative feedback on the HPO axis and affecting gonadotropin production.

This manifests as menstrual abnormalities and ovulatory dysfunction.

Obese women with a BMI >27 kg/m ² have a relative risk of anovulatory infertility of 3.1 (95% CI, 2.2–4.4) compared with their lean counterparts with a BMI 20.0–24.9 kg/m ² .

Obese women have a lower chance of conception within 1 year of stopping contraception compared with normal-weight women (i.e., 66.4% of obese women conceive within 12 months, compared with 81.4% of those of normal weight).

Multiple studies have demonstrated that obese women have increased time to pregnancy.

Obese women remain subfertile even in the absence of ovulatory dysfunction. Study showed reduced fecundity in eumenorrheic obese women and the probability of spontaneous conception declined linearly with each BMI point >29 kg/m ² .

In normogonadotropic anovulatory women, increased BMI and abdominal obesity are associated with decreased odd ratios of ovulation in response to clomiphene citrate.

In women with obesity, there is high rates of meiotic aneuploidy with fragmented disorganised meiotic spindles and improper alignment of chromosomes.

Obesity appears to disrupt the mitochondrial function in the oocyte.

There is also evidence of endoplasmic reticulum (ER) stress in the obese state.

The continued dietary excess of fatty acids accumulates in the tissues and exerts toxic effects, which is termed lipotoxicity.

Obese women have higher levels of reactive oxygen species (ROS) that induce mitochondrial and ER stress leading to apoptosis.

Lipotoxicity plays a role in the development of insulin resistance and a heightened inflammatory state.

Obesity is considered to be a chronic low-grade inflammatory state.

Obese women have higher circulating levels of C-reactive protein, a marker of systemic inflammation.

The developing blastocyst produces adiponectin, IL-1, and IL-6. The altered inflammatory milieu in obese women likely exerts an influence on follicle rupture at the time of ovulation and invasion of the trophoblast into the receptive endometrium.

This effect of obesity at the level of the oocyte could have downstream effects on endometrial receptivity and embryo implantation.

Obese women are more likely to create poor-quality embryos.

Embryos may also be susceptible to lipotoxicity.

Elevated leptin levels in obese women may exert a direct negative effect on the developing embryo.

Some studies suggest that decidualisation defects seen in obesity may contribute to compromised endometrial receptivity and poor implantation and may negatively affect the placentation process.

Many of the pregnancy complications seen in obese women are linked to placental dysfunction.

Studies found significantly higher spontaneous abortion rates in obese women.

In women with a history of recurrent pregnancy loss, obesity is a known risk factor for miscarriage in a subsequent pregnancy.

Chronic dysregulation of leptin pathways in obesity may negatively affect implantation.

Overweight and obese subfertile women have a reduced probability of successful fertility treatment.

Examination: The utility of the clinical examination is often limited in the obese woman, which results in a greater reliance on imaging.

Obese patients have difficult venous access.

Around the world, fertility treatment is withheld from women above a certain BMI, with a threshold ranging from 25 to 40 kg/m ² .

The proponents of this policy use three different arguments to justify their restrictions: risks for the woman, health and wellbeing of the future child, and importance of society.

The opponents feel that the obese women should be informed about the consequences and encouraged to lose weight. If, however, they are unable to lose weight despite effort, there should not be any argument to withhold their treatment.

Based on available evidence, it may be appropriate to consider morbid obesity as a contraindication for public-funded treatment where the aim is to maximise the value for money.

Obesity can contribute to missed diagnoses, nondiagnostic results, imaging examination cancellation because of weight or girth restrictions.

Recognition of equipment limitations, imaging artefacts, optimisation techniques, and appropriateness of modality choices is critical to providing good patient care.

In ovulatory but subfertile women, the chance of spontaneous conception decreases by 5% for each unit increase in the BMI.

National guidelines in the United Kingdom advise for a weight loss to a BMI of <30 kg/m ² prior to the start of any ovulation induction.

Overweight and obese women respond poorly to clomiphene induction and require higher doses of gonadotropins for superovulation.

Operators have encountered difficulty in completing the Hysterosalpingo Contrast Sonography procedures in obese participants, when the uterus was acutely retroverted or oblique, when loops of active bowel were present, or the adnexa were located beyond the penetration of the ultrasound signal.

Significant technical difficulty and increased radiation exposure have been associated with hysterosalpingography.

Laparoscopy and dye is not contraindicated in obese patients. Despite being associated with increased operating times, complication rates in obese patients are comparable to their nonobese counterparts. However, these procedures should be performed by a skilled surgeon in a special hospital setting.

The systematic review and metaanalysis suggest that antimullerian hormone and FSH are significantly lower in obese women and are inversely correlated with BMI.

There is limited number of published studies for any evidence supporting an association between BMI and inhibin B.

Antral follicle count does not appear to differ according to BMI.

With a goal of 10% weight loss, some studies had significantly higher conception rates and live birth rates (LBRs).

Other studies in obese women with PCOS, demonstrating improved ovulation and LBRs following lifestyle intervention and weight loss.

Current recommendations are to increase physical activity to at least 150 minutes weekly of moderate activity such as walking.

Physical activity has been shown to decrease systemic inflammatory mediators that may contribute to the improvement in fertility.

The perceptions that exercise can cause fatigue and it is a hard work as well as depression seem to decrease with continuation of an exercise programme in overweight infertile women.

Coached sessions of achievable frequency, for example, weekly, for up to 6 months should be considered to increase compliance.

Motivational interviewing techniques might also be useful. Dual enrolment may result in better adherence as partners tend to motivate each other.

A 500–1000 kcal/day decrease from usual dietary intake should lead to a 1- to 2-lb weight loss per week.

With a low-calorie diet of 1000–1200 kcal/day, achieving an average 10% decrease in total body weight over 6 months.

Adherence to ‘Mediterranean’ diet, characterised by higher intake of unsaturated fats, lower intake of animal fats, and lower ratios of omega-6 to omega-3 fatty acids for 2 years in patients with metabolic syndrome significantly decreases insulin resistance and serum concentrations of inflammatory markers.

Studies have been published extensively on the ‘fertility diet’, characterised by less consumption of trans fats and animal protein and more consumption of low-glycaemic carbohydrates, high-fat dairy, and multivitamins.

Bariatric surgery in women can restore menstrual regularity, correct ovulation, shorten folliculogenesis with ovulation, reduce serum testosterone levels, diminish percent body fat, and improve both sexual function and chance of pregnancy.

Surgically induced weight loss only partially improves deficient luteal progesterone production with a rise in LH secretion, suggesting the persistence of corpus luteum dysfunction.

Delaying pregnancy until 1–2 years after bariatric surgery has been recommended to avoid foetal exposure to nutritional deficiencies from rapid maternal weight loss.

A study examining pregnancy outcomes after bariatric surgery demonstrated lower risk of gestational diabetes and large-for-gestational-age infants. However, it also showed a concerning increased risk of small-for-gestational-age infants and a trend toward higher risks of stillbirth and neonatal death.

Bariatric surgery can be recommended for the women with a BMI of ≥35 kg/m ² .

Bariatric surgery does appear to improve the PCOS phenotype. Metabolic parameters, including insulin sensitivity and blood pressure, were also improved.

Women with PCOS are commonly (35%–80%) overweight (BMI >25 kg/m ² ) or obese (BMI >30 kg/m ² ).

Women in the United States with PCOS have a higher BMI than their European counterparts. Obesity may intensify the severity of the phenotypic characteristics of the PCOS, including disturbed menstrual cycle.

The severity of hyperandrogenism seems to be amplified in obese women with PCOS.

In obese women with PCOS, insulin resistance and hyperinsulinaemia are higher than in lean women with PCOS.

In the case of noncompliance, various treatments or interventions, including clomiphene citrate, gonadotrophins, insulin sensitizers, and laparoscopic ovarian drilling, are applied.

Oral medications used included orlistat, a lipase inhibitor; sibutramine, a selective serotonin and norepinephrine reuptake inhibitor; and acarbose, an alpha-glucosidase inhibitor shown to induce modest weight loss.

Metformin: the metaanalyses showed that weight-loss interventions have a nonsignificant advantage over metformin with respect to achievement of pregnancy or improvement of ovulation status.

Herbal: many obese women may also self-medicate with herbal supplements, although their safety and effectiveness have not been demonstrated.

Ephedra containing supplements have potentially life-threatening cardiovascular side effects and have been banned by the FDA.