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Effect of Obesity On Assisted Reproductive TOG 2017

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DOI: 10.1111/tog.

12343 2017;19:47–54
The Obstetrician & Gynaecologist
Review
http://onlinetog.org

Effect of obesity on assisted reproductive treatment


outcomes and its management: a literature review
a, b
Mohammed Khairy MD MRCOG, * Madhurima Rajkhowa MD MRCOG
a
Subspecialty Trainee of Reproductive Medicine and Surgery, Birmingham Women’s Fertility Centre, Birmingham Women’s NHS Foundation
Trust, Birmingham, West Midlands B15 2TG, UK
b
Consultant of Reproductive Medicine and Surgery, Birmingham Women’s Fertility Centre, Birmingham Women’s NHS Foundation Trust,
Birmingham, West Midlands B15 2TG, UK
*Correspondence: Mohammed Khairy. Email: mohammed.mahmoud@bwnft.nhs.uk

Accepted on 19 May 2016

Key content Learning objectives


 Obesity is associated with infertility and poor obstetric outcomes.  To understand the association of obesity and infertility with
 The current trends of advanced maternal age and rising obesity ART outcomes.
rates contribute indirectly to the growing demand for fertility  To learn the principles of obesity-related infertility management.
treatment and assisted reproduction treatment (ART), posing
Ethical issues
clinical and ethical dilemmas for fertility service providers.
 To understand the ethical challenges in the provision of ART for
 The live-birth rate, after ART, is significantly lower in obese
obese women and to inform the stance of professional bodies, such
women than non-obese women, possibly due to impaired oocyte
as the British Fertility Society and the European Society of Human
quality and/or defective endometrial receptivity. Poor ART
Reproduction and Embryology.
outcomes correlate positively with the severity of obesity.
 Management of obesity-related infertility should include diet, Keywords: assisted reproduction treatment (ART) / bariatric
exercise, cognitive behavioural interventions and possibly surgery / infertility / pregnancy / obesity
adjunctive pharmacotherapy. Bariatric surgery may benefit Linked resource: Single best answer questions are available for this
morbidly obese women who struggle to lose weight otherwise.
article at https://stratog.rcog.org.uk/tutorial/tog-online-sba-resource
 Randomised controlled trials are required to clarify the effects of
various therapeutic interventions for obesity on ART outcomes.

Please cite this paper as: Khairy M, Rajkhowa M. Effect of obesity on assisted reproductive treatment outcomes and its management: A literature review. The
Obstetrician & Gynaecologist 2017;19:47–54.

increasing number of overweight and obese women as well


Introduction
as older women will seek fertility interventions and may
Obesity is a major risk factor for many systemic conditions require assisted reproductive treatment (ART). This places
and has become a major public health problem as its strains in terms of resources and finances on the fertility and
prevalence has reached epidemic proportions. It is estimated obstetric services, in addition to raising the issue of ethics
that currently 26.1% of the adult female population in the regarding the eligibility of these patients for fertility
UK are obese with body mass index (BMI) >30 kg/m2 as treatment in the face of finite resources and potential harm
compared to 16.4% two decades ago.1 to both mother and baby.
It has been shown consistently that obesity has a strong In this article, we review the current evidence relating to
association with subfertility2–4 and is also a major risk factor different grades of obesity (overweight: BMI 25–29.9 kg/m2;
for serious pregnancy complications in mothers.5–8 obese class I: BMI 30–34.9 kg/m2; class II: 35–39.9 kg/m2; and
Moreover, there is an increase in the risk of early fetal class III: >40 kg/m2) and ART and seek to answer the
loss,9–11 congenital malformations12,13 and poor perinatal following questions:
outcomes as well as stillbirth and neonatal death.14–16 1. What is the evidence for the clinical outcomes of obese
Concurrent with this rising trend in obesity and obesity women having ART?
associated subfertility, is a trend of delaying childbearing. It is 2. How can obesity modify fertility and ART outcomes?
believed that this has led to increasing reliance on fertility 3. What are the potential interventions that may modify
treatment to achieve pregnancy. This means that an the outcomes?

ª 2017 Royal College of Obstetricians and Gynaecologists 47


Obesity and ART

4. Is it cost-effective to offer ART treatment to obese, (0.25–0.61) for BMI 35.00–39.99 kg/m2 and 0.32
subfertile women? (0.16–0.64) for BMI ≥40.0 kg/m2.20 Based in the results of
5. Is it ethical to refuse obese women fertility and ART this study, it was concluded that women with BMI >30 kg/m2
treatment options? have up to 68% lower risk of having a live birth
following their first ART cycle compared with women with
BMI <30 kg/m2.20
The clinical outcomes of ART in obese
The obstetric outcomes in obese pregnant women after
women
IVF have been reported using data for 60 232 singleton and
Information regarding the effect of obesity on ART outcomes 24 111 twin live births from the clinical outcome reporting
is derived mainly from retrospective observational system of the Society of Assisted Reproductive Technology
studies. The largest meta-analysis to date, that reported on (SART).21 There was a 1.5–2-fold increase in the risk of very
47 967 treatment cycles from 33 studies, concluded that early (<28 weeks) and early (<32 weeks) preterm birth
overweight or obese women had significantly lower clinical (VEPTB/EPTB) among singletons and a 2–3-fold higher risk
pregnancy rates (CPR) (relative risk [RR] = 0.90, P < 0.0001) of VEPTB/EPTB among conception of twins in obese women
and live-birth rates (LBR) (RR = 0.84, P = 0.0002) and (BMI >35 kg/m2) after IVF compared with similar
significantly higher miscarriage rates (RR = 1.31, P < 0.0001) conceptions in normal weight women.21
compared with women with a BMI <25 kg/m2.17 A subgroup
analysis of overweight and obese women separately
How can obesity affect fertility and ART
confirmed this conclusion, with a lower chance of LBR (RR
outcome?
= 0.91, 95% confidence interval [CI] 0.85–0.98) and (RR =
0.80, 95% CI 0.70–0.90) in the overweight and obese groups The association between obesity and infertility has long been
of women, respectively.17 recognised and several possible causative mechanisms have
The main strength of the findings of this meta-analysis is been suggested.
the consistency of results across studies showing worse
clinical outcomes in obese women as compared with normal Energy homeostasis and reproduction
weight women. The meta-analysis, however, did not adjust Research has shown that gut and adipose tissue hormones,
for the effect of potential confounders, such as age and which are the main controls of caloric intake, have a
polycystic ovary syndrome (PCOS), both of which are significant role in regulation of reproductive function. The
strongly associated with obesity, as well as other factors, most widely studied of the pancreatic and gut hormones are
such as smoking. Furthermore, the included studies had insulin, ghrelin and glucagon like peptide-1 (GLP-1), while
considerable heterogeneity in classifications of obesity and among the adipose tissue hormones, leptin and adiponectin
ovarian stimulation. are the best characterised.
Few studies have attempted to address these weaknesses. In In cases of high caloric intake with increased adipose
one study, obesity and age interaction was a significant tissue, the gut hormones (primarily insulin and GLP-1) and
predictor. At younger ages, a high BMI had a pronounced the adipose tissue hormone leptin act centrally in the
negative influence on fertility and this effect diminished as hypothalamus leading to a satiety response by inhibiting
the women aged.18 The finding of a greater effect of obesity neuropeptide Y (NPY). This inhibition of NPY together with
on fertility in younger women was corroborated by another stimulation of proopiomelanocortin (POMC) neurons
study in which obesity did not affect embryo development in relieves the effects of the inhibitory signals on the
women aged <38 years, although the CPR and LBR gonadotropin releasing hormone (GnRH) pulse generator
were reduced.19 in the hypothalamus. Leptin also stimulates the hypothalamic
A comprehensive regression analysis of 4609 women GnRH pulse generator directly through kisspeptin (an
stratified according to BMI categories in their first in vitro essential neuropeptide involved in the direct activation of
fertilisation/intracytoplasmic sperm injection (IVF/ICSI) GnRH neurons) with subsequent increases in gonadotropin
cycles and adjusted for multiple confounders, including levels, mainly luteinising hormone.22
age, ovarian reserve and response parameters, embryo quality Insulin and leptin seem to act synergistically, with the
and number of embryos transferred, showed significantly latter hormone being the main mediator of the stimulatory
decreased odds of implantation, clinical pregnancy, and live functions. Both insulin and leptin also act peripherally on the
birth in women with BMI >30 kg/m2. The adjusted odds ratio ovaries, where leptin potentiates insulin-induced theca cell
(AOR) for live birth was significantly lower across all proliferation and intra-ovarian androgen production.22
categories of high BMI compared with the normal weight On the other hand, circulating levels of the gut hormone
cohort, with AOR and 95% CI for live birth of ghrelin and the adipose tissue hormone adiponectin increase
0.63 (0.47–0.85) for BMI 30.00–34.99 kg/m2, 0.39 in cases of fasting, low caloric intake and malnutrition, while

48 ª 2017 Royal College of Obstetricians and Gynaecologists


Khairy and Rajkhowa

insulin and leptin levels plummet leading to inhibition of the (38% versus 20%; odds ratio [OR] 2.4, 95% CI 1.6–3.8).26
GnRH pulse generator in the hypothalamus and stimulation Furthermore, after adjusting for potential confounders, it was
of feeding behaviour.22 Teleologically, this mechanism helps found that having a BMI of >25 kg/m2 significantly increased
conserve energy during times of famine, while encouraging the risk of miscarriage after both fresh and cryothawed
reproduction when food is more readily available. blastocyst transfer by 2 and 6 fold, respectively.26
It is possible that obesity, as a state of prolonged hyper- It was also shown that women with a BMI of >30 kg/m2
caloric intake, leads to persistent activation of the GnRH and had significantly higher numbers of endometrial polyps
LH pulses centrally and theca cell proliferation peripherally, compared with women with a BMI of <30 kg/m2 (52% versus
leading to PCO/PCOS phenotypes. Alternatively, obesity may 15%). The degree of obesity was positively correlated with the
be the result of a state of leptin resistance, leading to lack of occurrence and size of the polyps, as well as the occurrence of
the satiety response. The associated hyper-insulinaemia in multiple polyps.27
these cases might lead peripherally to theca cell proliferation, Furthermore, an analysis of miscarriage karyotypes led
hyper-androgenaemia and PCO/PCOS. to the conclusion that overweight and obese women aged
A minority of morbidly obese patients have mutations in <35 years were less likely to have aneuploid miscarriages than
the leptin or leptin receptor genes leading to a complete lack women in a healthy weight range, suggesting alternative
of response to leptin with phenotypic features of obesity and mechanisms for miscarriage in this population.28 However,
hypogonadotrophic hypogonadism.23 in other studies, higher incidence of oocyte morphological
abnormalities,29,30 poorer response to ovarian stimulation, a
Obesity and inflammation requirement for higher dose of gonadotropins, lower
Another potential mechanism linking obesity and infertility is fertilisation rates and higher cancellation rates31–33 were
the effect of bidirectional communication between the found to be more common in obese women compared with
immune cells in adipose tissue and adipocytes leading to normal weight women. Another study showed that obese
release of free fatty acids (FFA) and various cytokines, as well women under the age of 35 years have lower quality embryos
as the induction of a systemic inflammatory response. This, with lower embryo utilisation rates and higher numbers of
together with intracellular accumulation of FFAs in various discarded embryos compared with age-matched normal
tissues, including ovarian tissues, leads to overproduction of weight women.34 These findings lend support to the theory
reactive oxygen species (ROS) and intracellular stress of lipotoxicity of oocytes and ovaries by accumulation of FFA
reactions, with associated damage and dysfunction of the and ROS and associated systemic inflammatory responses,
mitochondria and endoplasmic reticulum leading to suggesting the possibility of molecular/genomic defects in the
molecular defects of oocytes.24 oocytes of obese women.
The outcomes of ART cycles in obese women have A recent systematic review reported on the outcome of ART
provided some insight into the effect of obesity on fertility. cycles in obese oocyte recipients with a BMI of >30 kg/m2.
Lower embryo implantation rates have been reported in This study has shown no significant effect of obesity on the
obese women compared with those of normal weight women, rates of clinical pregnancy, implantation or miscarriage. This
despite a lack of differences reported in oocytes and embryo may imply a predominant role of oocyte dysfunction over
quality and the percentage of blastocyst transfers. This endometrial receptivity in obese women.35
suggests the existence either of molecular or genomic
defects in the oocytes or embryos of obese women, or an
Potential interventions in obese women
effect of obesity on endometrial receptivity.10 Analysis of
prior to ART
implantation rates among recipient women in different BMI
categories following oocyte donor IVF cycles using good There is a paucity of randomised controlled studies of
quality embryos has shown a trend of lower implantation interventions aimed at improving outcomes in obese women
rates in women in the higher BMI group, suggesting an pursuing fertility treatment in general and ART in particular.
endometrial effect.11 Here, we address the therapeutic interventions to optimise
In support of the endometrial effect, multivariable outcomes in obese women undergoing infertility treatment
regression analysis of the results of a study of healthy term under the following subheadings: diet and lifestyle, medical
births following single blastocyst transfer revealed that management, and surgery.
increasing BMI and smoking are significant negative
predictors of healthy term births independent of maternal Diet and lifestyle
age.25 Similarly, a retrospective analysis of fresh and The latest National Institute of Health and Care Excellence
cryothawed single blastocyst transfers showed that women (NICE) guidelines on management of obesity recommends
with a BMI of >25 kg/m2 have double the risk of miscarriage that the treatment of obese women should be tailored
at <23 weeks compared with women with a normal BMI according to risk stratification based on BMI/waist

ª 2017 Royal College of Obstetricians and Gynaecologists 49


Obesity and ART

circumference and associated comorbidities (e.g. diabetes, adherence to the dietary recommendations with
hypertension, dyslipidaemia, cardiovascular disease and improvement of the PDRS by one point, was associated
obstructive sleep apnoea),36 with female waist with a 65% increase in the ongoing pregnancy rate.40
circumference of <80 cm considered low risk, 80–88cm It seems therefore, that there is scope for improving
categorised as high risk, and >88 cm as very high risk. outcomes for overweight and obese women undergoing ART
Dietary modification and regular exercise aimed at by lifestyle interventions; however, there is a gap in evidence
restriction of caloric intake and increased energy from randomised controlled trials.
expenditure remain the first line and cornerstone of
management of obesity in general. The main principle of Medical management
dietary modification is a low caloric intake with a Pharmacotherapy should be offered as an adjunct rather than
recommended daily caloric intake of 600 kcal less than as a substitute to diet and exercise management to women
caloric requirement to maintain a stable body weight. Very who have achieved partial success in losing weight and
low-calorie diets (<800 kcal/day) should not be used persevered with lifestyle changes for 6 months. There are
routinely and if used in cases of emergency, the diet should several classes of medications used for weight loss and none
be nutritionally complete and followed for a maximum of have been shown to be superior to the others. The average net
12 weeks. Physical activity should be of moderate intensity weight loss after 7–48 weeks of treatment achieved in one
for at least 60–90 minutes on five or more occasions each meta-analysis was 2–4 kg after subtracting weight loss
week. Furthermore, activities should be of a type that can be associated with the placebo.41 Combining medical
incorporated into the daily routine, such as brisk walking, treatment with lifestyle interventions may lead to greater
cycling, gardening or supervised exercise programmes. The weight loss.
weight-loss target should be set realistically at no more than A number of classes of medications can be used for weight
0.5–1 kg/week and should be agreed individually with loss. Anti-absorptive drugs include orlistat (Xenical), which
each woman.36 is a potent inhibitor of pancreatic lipase leading to
The main challenge is to introduce behavioural changes interference with the absorption of fat and fat soluble
that lead to long-term adherence to the modified diet and vitamins from the gut. The recommended dose is 120 mg
exercise regimen as weight is inevitably regained when taken immediately before, during, or up to 1 hour after each
lifestyle changes are not sustained. Therefore, there may be meal (maximum 120 mg three times daily). Common side-
a role for cognitive and behavioural interventions in effects include flatulence, oily leakage from the rectum with
combination with dietary and exercise modifications to steatorrhoea and fecal urgency. Prolonged administration can
achieve long-term effects. Cognitive behavioural strategies lead to malabsorption, and vitamin deficiency syndromes.
that have been suggested to help adults achieve weight Orlistat should, therefore, be used for longer than 12 weeks
control include self-monitoring of behaviour and progress, only if weight loss exceeds 5% of the initial bodyweight and
stimulus control, goal setting, slower eating, social support, after counselling patients about the potential risks
problem solving and assertiveness, cognitive restructuring and benefits.42
(thought modification) and reinforcement of change to Insulin-sensitising agents, such as metformin, decrease
prevent relapse.36 The importance of a multidisciplinary circulating insulin and androgen levels and may be
approach to lifestyle interventions aimed at combating associated with a modest decrease in body weight and
obesity has recently been re-emphasised, as no single visceral fat. Two studies have shown benefit from
intervention seems to be effective for long-term control.37 combining metformin with a hypocaloric diet for reducing
Two small-scale dietary trials on the effect of very low- weight and visceral fat.43,44 However, the effectiveness of
calorie diet (VLCD) and low-calorie diet (LCD) before IVF metformin alone for reducing weight in obese PCOS
have been reported. The former study included a very small patients has not been demonstrated.45 Moreover, when
number of women, precluding any meaningful conclusion.38 metformin is used as adjunctive treatment for ovulation
The latter study compared LCD and exercise versus no induction in PCOS patients, it is more effective in those
intervention for a period of 6–8 weeks. Although weight that are lean than it is in obese PCOS patients. The
reduction and BMI changes were statistically significant, recommended dose is 1500–2000 mg/day and the main
there was no statistically significant difference between LBRs side-effects are gastrointestinal upset and rarely, lactic
in the two arms of the study.39 acidosis in patients with hepatic and renal impairment. In
One observational study has shown that the Preconception the UK, metformin is not licensed as an anti-obesity drug
Dietary Risk Score (PDRS), which is a measure of nutritional and although it has been widely used in management of
habits and dietary quality (higher scores indicate higher PCOS, this is still an unlicensed indication.
dietary quality), is an independent predictor of ongoing Other classes of anti-obesity drugs include appetite
pregnancy after IVF treatment.40 In the same study, an suppressants such as sibutramine and the cannabinoid

50 ª 2017 Royal College of Obstetricians and Gynaecologists


Khairy and Rajkhowa

receptor antagonists (e.g. rimonabant), have been withdrawn BMI of >40 kg/m2 can be expected to lose 20–40 kg over
from the market in the UK due to concerns over 2 years and to maintain their reduced weight for 10
cardiovascular effects (hypertension, palpitation) for the years.48–50 Pregnancy is therefore generally not
former class and neuro-psychiatric effects including recommended for 12–18 months after bariatric surgery,
depression and suicidal risks of the latter class. when most of the weight loss occurs, to avoid nutritional
The safety of exposure to anti-obesity drugs in early deficiencies. These women should receive a follow-up care
pregnancy has been assessed using the Swedish National package for a minimum of 2 years, including monitoring of
Medical Register including the data for 392 126 infants. No nutritional intake, physical activity and comorbidities and
evidence of any increase in the relative risk of major the provision of psychological support.36
malformation was observed in women who used orlistat in Evidence of the effects of bariatric surgery on infertility
early pregnancy (248 women) (RR = 0.42, 95% CI 0.11– and IVF is sparse, with only a small amount of data regarding
1.07).46 It is, however, recommended that anti-obesity drugs IVF outcomes after bariatric surgery available from case–
are stopped once pregnancy is achieved. control studies of a small number of patients; therefore, more
One small randomised controlled trial (RCT) comparing high-quality studies are needed.51 There are no reports of
metformin and orlistat in obese anovulatory PCOS patients RCTs assessing the impact of bariatric surgery in infertile
for 3 months showed no significant difference in ovulation populations generally or in patients undergoing ART;
rates between the two treatments, although significant however, a recent observational study has shown an
reductions in BMI and androgen levels were observed in improvement in the number of oocytes retrieved in obese
both arms of the study.47 Currently, there are no reports of women after bariatric surgery.52
RCTs comparing anti-obesity drugs with placebo in an
IVF setting.
Is it cost-effective to offer ART to obese
subfertile women?
Bariatric surgery
These operations are increasingly being used for the The cost-effectiveness of ART treatment in obese women in the
treatment of obesity and are classified into three categories. UK has been addressed by Scottish investigators who estimated
the direct health service costs of live birth after a single cycle of
 Restrictive surgery (vertical band gastroplasty, adjustable
IVF treatment among women in different BMI categories.
gastric banding, intragastric balloon, laparoscopic gastric
They concluded that there is no statistically significant
plication, sleeve gastrectomy) is aimed at restricting gastric
difference in the obstetric costs among the different BMI
capacity and inducing early satiety.
groups. The authors held this view mainly for class I obese
 Largely restrictive/mildly malabsorptive surgery (e.g.
women compared with the normal BMI group and maintained
Roux-en-Y gastric bypass) is aimed at both restricting
that the small number of women included in higher BMI
gastric capacity and reducing the length of
groups led to uncertainty regarding their conclusion.53
absorbing bowel.
Another study modelled the costs of achieving live birth in
 Largely malabsorptive/mildly restrictive surgery (e.g.
both ovulatory and anovulatory obese women using different
biliopancreatic diversion duodenal switch). Although
modalities of infertility treatment as compared with women
gastric capacity is reduced in these procedures the main
with normal BMIs. In their hypothetical model based on an
effect of surgery is inducing a state of malabsorption.
extensive literature search of reported success rates of
The primary goal of bariatric surgery is to ameliorate different treatments they included the direct costs of
medical problems related to obesity. These operations treatment and indirect costs of pregnancy complications.
are therefore generally offered to women with a BMI of They concluded that the costs per live birth in anovulatory
>40 kg/m2 or >35 kg/m2 with serious coexisting medical overweight and obese women were 54% and 100% higher,
complications aggravated by obesity and who are highly respectively, than those in their normal weight counterparts,
motivated but have struggled to achieve their target body and for ovulatory obese women the costs were 44% and 70%
weight with conventional dietary and behavioural therapy. higher, respectively.54
The NICE guidelines recommend early consideration of
bariatric surgery in patients with a new diagnosis of type II
Is it ethical to withhold fertility treatment
diabetes and BMI 30–35 kg/m2 and even lower BMI in
and ART options from obese women?
patients of Asian origin.
The women selected should be fully aware of the The results of economic analyses regarding the cost-
complications associated with the operation, including an effectiveness of ART treatment in obese women are
overall mortality rate of 1%.48–50 Data from multiple conflicting. Furthermore, there is a paucity of data for the
meta-analyses indicate that women with a preoperative efficacy of ART outcomes in higher classes of obesity.

ª 2017 Royal College of Obstetricians and Gynaecologists 51


Obesity and ART

Consequently, it is still ethically contentious to justify In 2010, The European Society of Human Reproduction
declining ART treatment from this group of women based and Embryology (ESHRE) also issued a statement
on current data. regarding lifestyle factors and access to medically assisted
There is a potential conflict between the patient’s right of conception. The position of the ESHRE is that it is not
autonomy on the one hand and the societal perspective of unethical for fertility specialists to insist on serious
justice as well as the physician’s professional perspective of efforts to achieve weight loss before treatment can
providing the highest level of care on the other. be considered.56
Arguments for offering ART treatment to obese The NICE guidelines on fertility management recommend
women include: that women should have a BMI of 19–30 kg/m2 before
commencing ART as BMIs outside this range are likely to
i. Respect for patient’s autonomy if the woman is willing to
reduce the success of the treatment.57
accept an unfavourable outcome.
In conclusion, it seems that a conditional offer of fertility
ii. Withdrawal of treatment from obese women is an act of
treatment to obese women based on achievement of a target
injustice and discrimination compared with other obese
weight is justifiable. There are, however, a number of
women who conceive naturally.
unresolved ethical questions. For instance, is it justifiable to
The arguments against offering unconditional ART require older women to achieve the same body weight targets
treatment are: as younger women given the decline in fertility with age? At
what level of obesity should treatment be withheld? How
i. Physicians have an ethical duty to provide high-quality
would an infertility specialist decide if a woman has made
care and avoid harm in their professional capacity.
genuinely serious efforts to lose weight? Furthermore, would
Therefore, a requirement for weight loss is, in fact, in the
it represent better use of resources to offer bariatric surgery
interests of both the mother and the child and is in
to women who have struggled for years to lose weight and
accordance with the principle of non-maleficence
their fertility is in decline rather than to offer IVF treatment?
without violating the woman’s autonomy.
ii. Requiring obese women to adopt a healthy lifestyle and
achieve a certain weight target is neither impossible nor Conclusion
unfair as the success rate of ART can improve with BMI
In summary, obesity has a significantly adverse effect on ART
reduction. Furthermore, without these changes, these
outcome independent of age and other confounders. This
women will have high risk pregnancies as well as a high
effect seems to be more pronounced in younger women
risk of short- and long-term health problems in their
(aged <35 years). The effect of obesity on ART outcome
offspring. It is, therefore, professionally responsible to
seems to be mediated by both molecular changes in oocytes
require lifestyle changes to reduce the risk of harm. It is
leading to lower quality embryos as well as by impairment of
also justifiable from a societal perspective to reduce the
endometrial receptivity.
inevitably increased demand on resources. Supporters of
Unfortunately, there is paucity of data from
the latter argument maintain that comparing women
interventional studies that assess the effectiveness of
requiring ART with those who conceive naturally is not a
different interventions on outcome in obese women
valid argument because as all cases should be similar in
undergoing fertility treatment. Thus, further well-designed
all relevant aspects if differential treatment is to be called
studies in this area are required. There is also a need for a
unjust. Although obese women who conceive naturally
shared care pathway involving GPs or specialised bariatric
are advised to reduce weight and adopt a healthy lifestyle
units and infertility services.
preconception, they do not require medical attention to
The cost-effectiveness of ART in obese women is still an
achieve pregnancy.
unresolved issue. However, as obesity is a modifiable risk
As there is no hierarchy of evidence in ethical studies that factor, it would seem reasonable and ethically justifiable to
inform practice, the collective opinion of professional bodies require obese women to lose weight before receiving ART.
is regarded as the best available source of advice on offering
fertility treatment. Disclosure of interests
In 2007, the British Fertility Society issued guidelines There are no conflicts of interest.
on offering fertility treatment to obese women, which
recommended that women seeking fertility treatment Contribution to authorship
should have a BMI of <35 kg/m2. In addition, when MK reviewed the literature, wrote the manuscript and revised
clinical circumstances permit, treatment of younger the final draft after critical appraisal by MR. MR reviewed the
women should be delayed until a BMI of <30 kg/m2 draft manuscript critically and revised the content before
is achieved.55 final approval.

52 ª 2017 Royal College of Obstetricians and Gynaecologists


Khairy and Rajkhowa

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fertilization: a retrospective cohort study using the Society for Assisted
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