Obesity in women and it's bad effect on fertility and hypertension and stroke in later age

The ill-effect of Obesity in Reproductive Performance both in Males as well as Females. Obesity induces sub-fertility, an ovulation, miscarriage rate and enhanced congenital abnormalities. Below is the evidence for your judgement.

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Defining Obesity and the Extent of the Problem

A normal body mass index (BMI) is considered to be 19-24.9 kg/m2, although some would consider the lower limit of normal to be 20kg/m2. Being underweight leads to hypothalamic amenorrhoea and increases risk to pregnancy if conception does occur. For consistency, we refer to overweight as a BMI > 25 kg/m2 and obese as a BMI > 30 kg/m2.

DEFINITIONS OF BMI RANGES

Overweight >25 kg/m2

Pre-obese 25.0-29.9 kg/m2

Moderate obesity (class I) 30.0-34.9 kg/m2 Severe obesity (class II) 35.0-39.9 kg/m2

Very severe (morbid) obesity (class III) >40 kg/m2

BMI is a reproducible measurement that is easy to measure. However, in metabolic terms, the distribution of body fat is more important than actual body weight. Visceral fat is more metabolically active, and an increased waist circumference (or waist: hip (W: H) ratio) correlates better with both metabolic risk and long-term disease. Unfortunately, waist circumference is difficult to measure (i.e. subject to increased error) in obese individuals, whereas BMI is more consistent.

Insulin resistance is also an important correlate of BMI and is perceived as a more accurate marker of the metabolic effect of obesity. There are also important ethnic variations in the expression of insulin resistance. A BMI > 30 kg/m2is usually considered to confer increased risk in white Caucasians, whereas in those of South Asian origin a BMI > 25 kg/m2is sufficient to increase risk of metabolic defects.

Obesity and Reproduction

Insulin resistance is defined as a reduced glucose response to a given amount of insulin and may occur secondary to resistance at the insulin receptor, decreased hepatic clearance of insulin and/or increased pancreatic sensitivity. The measurement of insulin resistance is an imprecise science without universally accepted guidelines. Technical difficulties have given rise to many invasive tests, including the euglycemic clamp method. This method is considered to be a 'gold standard', but it is complex and expensive, as are the measurements of fasting insulin concentrations, which combined with glucose can provide formulae for the homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI) calculations of insulin resistance. So, in practice, these tests are confined to the research setting in the United Kingdom and have not become established in clinical practice in repro­ductive medicine. Most clinicians resort to the standard 75-g oral glucose tolerance test (Oral glucose tolerance test (OGTT); Fasting glucose levels alone are poorly predictive of 2-h levels in impaired glucose tolerance (IGT), suggesting that a full OGTT should be conducted. Between 20% and 40% of women with polycystic ovary syndrome (PCOS) have IGT, a value that is significantly higher than the preva­lence among age- and weight-matched pre-menopausal women.

In a U.K. study of pre-menopausal women with non-insulin-dependent diabetes mellitus (NIDDM), almost 30% had PCOS and 82% had polycystic ovary (PCO) morphology. Women with PCOS are between three and seven times more likely to develop NIDDM than control subjects. Furthermore, the conversion rate is potentially rapid. When 54 normoglycemic women and 13 women with IGT at baseline with PCOS were followed for an average of 6.2 years, 9% of the former group developed impaired tolerance and 8% developed frank NIDDM. Of the IGT group, 54% had frank NIDDM at follow-up. BMI at baseline was an independent significant predictor of conversion. The speed of change suggests regular surveillance is required; especially when BMI is high, yet this surveillance is far from becoming part of standard U.K. healthcare for these women.

Although the insulin resistance may occur irrespective of BMI, the common association of PCOS and obesity has a synergistic deleterious impact on glucose homeostasis and can worsen both hyperandrogenism and anovulation. An assessment of BMI alone is not thought to provide a reliable prediction of cardiovascular risk. It has been reported that the association between BMI and coronary heart disease almost disappeared after correction for dyslipidemia, hyperglycaemia and hyper­tension. Some women have profound metabolic abnormalities in the presence.

Definitions of Glucose Tolerance after a 75-g Glucose Tolerance Test

                                                      Diabetes Mellitus        Impaired Glucose Tolerance                    Impaired Fasting Glycaemia        

Fasting glucose (mmol/L)        >7.0                          <7.0                     >6.1 and <7.0                                             

2-h glucose (mmol/L)              >11                         >7.8, <11.1               <7.8

 Action                   Refer diabetic clinic              Dietary advice check fasting glucose annually Consider metformin               Dietary advice check fasting glucose annually of a normal

BMI, whereas others have few risk factors despite an elevated BMI. Thus, rather than BMI itself, it is the distribution of fat that is important, with android obesity being more of a risk factor than gynaecoid obesity. Hence, the value of measuring W: H ratio, or waist circumference, detects abdominal visceral fat rather than subcutaneous fat. It is the visceral fat that is metabolically active, and when increased, it results in increased rates of insulin resistance, type 2 diabetes, dys­lipidemia, hypertension and left ventricular enlargement. Exercise has a significant effect on reducing visceral fat and reducing cardiovascular risk. There is a closer link, between waist circumference and visceral fat mass, as assessed by computed tomography (CT) scan, than with W:H ratio or BMI. Waist circumference should ideally be less than 79 cm, whereas a measurement that is greater than 87 cm carries a significant risk.

Effect of Obesity on Pregnancy

(Miscarriage, Maternal Health, Fetal Health)

Miscarriage rates appear to be increased with increasing maternal weight. In those women who conceive naturally, there is an increased risk of miscarriage if they are moderately overweight (BMI 25-27.9 kg/m²). This relationship also has been demonstrated in women who conceive by in vitro fertilisation (IVF) or who are recipients of donated oocytes.

There is also an increased rate of insulin resistance in women with recurrent miscarriage (27% compared with 9.5% in controls with ongoing pregnancies). This finding introduces the notion that it is the metabolically active fat, that is, visceral fat, that is most important in predicting reproductive outcome. A possible mecha­nism is via plasminogen activator inhibitor (PAI-1), a potent inhibitor of fibrinolysis that is elevated in insulin resistance, PCOS and women who miscarry. There are several other possible mechanisms, including adverse effects of insulin resistance on follicular development, oocyte maturation and endometrial development

Pregnancy carries significant risks for those women who are obese, with increased rates of congenital anomalies, including neural tube (odds ratio (OR) 3.5), omphalocele (OR 3.3) and cardiac (OR 2.0) defects; miscarriage; gestational diabetes; hypertension and problems during delivery.

The risks of congenital anomalies appear real, although there are also techni­cal difficulties in assessing the fetus by ultrasound because adipose tissue attenu­ates the signal. Pregnancy itself exacerbates any underlying insulin resistance; as a result, women with PCOS, obesity or both have an increased risk of gestational diabetes.

Obesity is associated with an increased risk to the mother during pregnancy. Risks include increased incidence of hypertension, gestational diabetes and thromboembolic disorders as well an increased cesarean section rate. Macrosomia, admission to neonatal intensive care, birth defects, stillbirth and perinatal death are all increased in the infants of women who are obese. In a U.K. study of 287,213 singleton pregnancies, 176,923 (61.6%) were of normal weight (BMI 20-24.9) and 31,276 (10.9%) were obese (BMI > 30).

Risk during Pregnancy in Obese Women

Condition                                                                 Odds Ratio (95% Confidence Interval)

Gestational diabetes                                                                   3.6(3.25-3.98)

Pre-eclampsia                                                                          2.14(1.85-2.47)

Induction of labour                                                               1.70(1.64-1.76)

Cesarean section                                                                          1.83(1.74-1.93)

Post-partum haemorrhage                                                             1.39(1.32-1.46)

Genital infection                                                                            1.3(1.1-1.6)

Urinary tract infection                                                                  1.4(1.2-1.6)

Wound infection                                                                             2.2(2.0-2.6)

Macrosomia                                                                            2.36(2.23-2.50)

Intrauterine death                                                                        1.4(1.14-1.71)

In a study of

women with PCOS undergoing ovulation induction, of 270 with a BMI > 35 kg/m², there were only five pregnancies of which one was stillborn and another had congenital anomalies .The proposed mechanisms that increase the stillbirth and congenital anomaly rate include insulin resistance and incipient or undi­agnosed diabetes. Similar trends have been shown in an Australian population of women giving birth, with a doubling of birth defects from 1.9% in women with a BMI of 30-40 kg/m² to 4% in women with a BMI of > 40 kg/m². There is also evidence that obesity in pregnancy causes programming of the fetus to become obese in later life.

Pregnancy in obese women is therefore more costly because of increased cesarean section rates, length of stay and admission to neonatal services. Overweight mothers are more likely to have hypertension and thromboembolism, leading to a higher risk of maternal mortality. In 2000-2002, of the 261 deaths reported to the U.K. Confidential Enquiry into Maternal Health, 78 women (35%) were obese, compared with 23% of women in the general population, and of these women more than one-quarter had a BMI > 35 kg/m². A gain in weight between first and second pregnancies, even if maternal BMI remains within the normal range, has been shown to significantly increase the risk of gestational diabetes, pre-eclampsia and stillbirth .

 

Influence of obesity on Natural Fertility

Body weight has a profound effect

on the initiation of puberty in girls and their subsequent natural fertility. A detailed account is beyond the scope of this book, and there are some excellent reviews that include appraisals of the interrelationships between centrally acting hormones and active products of adipose tissue. Although most attention has been directed towards the effects of obesity on anovula­tory infertility, there is evidence that being overweight can influence spontaneous conception in women who are ovulating. Again, it is central/visceral fat that appears to be most significant.

Waish: Hip (W:H) Ratio and Percent Pregnant after 12 Cycles

           W: H ratio                                                                   %Pregnant after 12 Cycles

<0.70                                                                                                       63

0.7-0.75                                                                                                    51

0.76-0.8                                                                                                     47

0.81-0.85                                                                                                   41

>0.85                                                                                                        32

Source: Zaadstra BM et al, BMJ 305,484-7,1993