Obesity has reached epidemic proportions throughout many parts of the world and it poses significant health and economic burdens to both developed and developing societies.
This rise in obesity is not restricted to older generations, with one in five women and men of reproductive age obese.
The effect of obesity on female reproductive capacity has been widely appreciated through the classical association with polycystic ovarian syndrome (PCOS).
Recent trials focusing on metformin alone, or in combination with clomifene, have failed to demonstrate a beneficial effect over clomifene alone in the treatment of PCOS-associated infertility.1
Consequently, greater attention is being placed on lifestyle modification, with weight loss being the primary step in management of obese women affected by PCOS.
Preconceptual weight loss
Given the adverse impact of obesity on both spontaneous and IVF outcomes, targeted lifestyle intervention and optimisation of pre-pregnancy weight is applicable to all women planning pregnancy.
However, adequate preconceptual attainment of weight loss is difficult, with recent large scale trials of caloric restriction reporting reductions in BMI of around 2kg/m2 at six months.2
In a society which restricts state-funded assisted conception to women based on BMI criteria (≤30kg/m2 or 35kg/m2 depending on the PCT) for many obese women the prospect of attaining this through lifestyle modification is small and, if achieved, is likely to be after several years with the concomitant age-related reduction in IVF success rates.
Furthermore, although very-low-calorie diets (500kcal/day) can induce substantive weight loss, they are associated with reduced spontaneous conception and increased risk of pre-term birth.3
Notably, the only study that undertook this approach prior to IVF was stopped after 10 recruits due to the detrimental impact on oocyte yields and fertilisation rates.4
Alternative strategies need to be considered. For many private IVF clinics this is simply a higher or no BMI limit. However, this approach results in pregnancies in morbidly obese women with all their inherent maternal and perinatal complications.
An alternative approach for morbidly obese women would be preconceptual bariatric surgery.
Irrespective of the type of surgery, young women who undergo bariatric surgery attain massive weight loss and for many they experience normalisation of their menstrual cycle, enhanced sexual function, improvement of their metabolic profile, including their diabetes and cardiovascular risk, and achieve pregnancies, but with a reduced risk of miscarriage and pregnancy complications.5
Although at present it is not known whether assisted conception outcomes will also improve, it is clear that obese women require increased doses of gonadotrophins, produce fewer oocytes and good quality embryos and have an increased miscarriage risk, all of which contribute to a reduced probability of a live birth.6
Timing of surgery
The timing of surgery and a subsequent pregnancy are likely to be critical, given the detrimental effects of acute weight loss on assisted conception.
One option would be to consider infertility as a significant comorbidity and initiate bariatric surgery early in the infertility treatment pathway, but combine with barrier contraception during the initial months of weight stabilisation.
Although the use of contraception in couples trying to conceive may be counterintuitive, this is not dissimilar to the approach currently advocated for folic acid.
It will also minimise the risk of the initial small changes in weight loss inducing ovulation and thereby pregnancy while still morbidly obese.
The long-term cost-effectiveness of preconceptual bariatric surgery compared with a treat-all approach is unknown but will inevitably influence clinical decision making.
Paternal reproductive health
Although classically overlooked, the impact of obesity on paternal reproductive health is of increasing importance. It is clear from several epidemiological studies that there is a dose-dependent adverse effect of male obesity on fecundity.
The altered hormonal milieu and pro-inflammatory state of male obesity combined with scrotal lipomatosis are likely to play major roles in the pathophysiology of impaired spermatogenesis.
Moreover, obesity is closely related to erectile dysfunction, with 79 per cent of affected men either overweight or obese.
Despite this growing problem, at present the role of lifestyle modification or surgery on male reproductive function is unknown.
The impact of both obesity and related metabolic perturbances on reproductive health is profound and affects both genders and all generations.
Public health measures to support healthier food choices and to reduce sedentary lifestyles are of course welcome but will take time to reverse current trends in obesity levels.
Of course, advice for achieving a healthy lifestyle should also be actively disseminated by all healthcare professionals at every opportunity, including the gynaecology clinic and antenatal and postnatal visits. Ideally, the risks of conceiving when obese should be disseminated through public health initiatives.
In the meantime, we must prioritise our target medical interventions to those at greatest risk and use proven therapies and interventions to mitigate risks associated with obesity.
Finally, lifestyle intervention is the preferred method to lose weight but for the morbidly obese bariatric surgery early in their infertility pathway may prove to have the biggest impact on fertility and pregnancy outcomes.
- Professor Nelson is Muirhead Chair in obstetrics and gynaecology at the University of Glasgow
1. Legro RS, Barnhart HX, Schlaff WD et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007; 356: 551-66.
2. Sacks FM, Bray GA, Carey VJ et al. Comparison of weight-loss diets with different compositions of fat, protein and carbohydrates. N Engl J Med 2009; 360: 859-73.
3. Bloomfield FH, Oliver MH, Hawkins P et al. A periconceptional nutritional origin for noninfectious preterm birth. Science 2003; 300: 606.
4. Tsagareli V, Noakes M, Norman RJ. Effect of a very-low-calorie diet on in vitro fertilization outcomes. Fertil Steril 2006; 86: 227-9.
5. Maggard MA, Yermilov I, Li Z et al. Pregnancy and fertility following bariatric surgery: a systematic review. JAMA 2008; 300: 2286-96.
6. Maheshwari A, Stofberg L, Bhattacharya S. Effect of overweight and obesity on assisted reproductive technology: a systematic review. Hum Reprod Update 2007; 13: 433-44.