Hindawi Publishing Corporation
Journal of Obesity
Volume 2016, Article ID 1871594, 6 pages
http://dx.doi.org/10.1155/2016/1871594
Review Article
Bariatric Surgery, Polycystic Ovary Syndrome, and Infertility
James Butterworth,1 Jean Deguara,2 and Cynthia-Michelle Borg1
1
University Hospital Lewisham, Lewisham and Greenwich NHS Trust, London, UK
Kingston Hospital NHS Foundation Trust, Kingston upon Thames, UK
2
Correspondence should be addressed to Cynthia-Michelle Borg; cynthia.borg@gmail.com
Received 28 August 2016; Revised 16 October 2016; Accepted 18 October 2016
Academic Editor: John B. Dixon
Copyright © 2016 James Butterworth et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Background. Polycystic ovary syndrome (PCOS) is the commonest cause of female infertility. Visceral obesity and insulin resistance
are key pathophysiological mechanisms behind PCOS. Women suffering from this syndrome and infertility often seek bariatric
surgery hoping that they would be able to conceive postoperatively. Objective. At present, there is no consensus on the role of
bariatric surgery in the management of PCOS-associated infertility within the medical community, making it difficult to give
specific advice to these women, so a review of the literature was necessary. Results. A detailed review of the literature was performed.
Only 6 manuscripts were relevant and contained quantitative data. They demonstrated that bariatric surgery results in postoperative
conception rates varying from 33% to 100%. Surgery is also associated with amelioration of menstrual irregularities, hormonal
abnormalities, and hirsutism that are associated with PCOS. These studies were retrospective and only had a small number of
participants with infertility. Conclusions. Bariatric surgery has been shown to conclusively improve life expectancy, quality of life,
and comorbidities like type 2 diabetes and obstructive sleep apnea. However, further research is required to identify whether weight
loss surgery results in significant improvement in fertility of women with PCOS and to investigate which operation has the best
results.
1. Introduction
Polycystic ovary syndrome (PCOS) is the most frequent cause
of female infertility. The Rotterdam criteria are often used
to make a diagnosis of PCOS. These include the presence
of at least two of the following: clinical and/or biochemical
features of hyperandrogenism, menstrual dysfunction, and
the appearance of polycystic ovaries on ultrasound, once
other endocrine conditions have been excluded [1]. Other
criteria that can be used include those from the National
Institutes of Health (NIH) and the Androgen Excess Society
(AES) [2]. PCOS has estimated prevalence of over 10% in
women of childbearing age [2]. Besides being associated with
infertility, PCOS is also associated with a higher incidence of
type 2 diabetes mellitus (T2D), endometrial carcinoma, and
cardiovascular disease including stroke and coronary heart
disease.
The exact etiology of PCOS is unknown and probably
represents a complex interaction between environmental and
genetic factors. Insulin resistance and hyperinsulinaemia
are thought to be key pathophysiological mechanisms.
More than 50% of females with this syndrome are obese.
Obesity in women of childbearing age is associated with
anovulation, infertility, pregnancy loss, pregnancy-associated
complications such as preeclampsia and gestational diabetes,
and postpartum complications including hemorrhage as well
as higher rates of infant mortality and congenital defects
[3, 4]. Obesity in patients with PCOS is also associated with
delayed or failed response to fertility treatments including
clomiphene citrate, gonadotropins, and assisted insemination
[5, 6]. The British Fertility Society advises that fertility
treatment should be deferred until women have a body mass
index (BMI) of less than 35 or BMI under 30 if they are below
37 years of age [7]. Metformin and nonsurgical weight loss
measures have been advocated as first-line management for
PCOS [8, 9]. It has been suggested that even a modest loss of
up to 5% of the initial body weight can result in spontaneous
ovulation, restoration of menstrual cycle regularity, and
pregnancy in obese women with PCOS [10–12].
2
Bariatric surgery is the most durable and effective
treatment for morbid obesity and also results in the
improvement of the metabolic syndrome. With the safety
of the laparoscopic approach and improved understanding
of the metabolic changes occurring in bariatric patients
postoperatively, morbidly obese women with infertility
secondary to PCOS have resorted to bariatric surgery [13].
Historically, epidemiological studies have suggested that the
rapid weight loss in the first year or two after bariatric
surgery may increase women’s chance of conception. While
the incidence of PCOS decreases significantly after surgery
[14], there are very few studies assessing fertility before and
after bariatric operations. At present, there is no consensus on
the role of such surgery in the management of infertility and
whether surgery can also be beneficial in women who have a
BMI of under 40 kg/m2 .
In this article, we systematically review the published
literature to assess the effects of bariatric surgery on fertility
in women with PCOS.
2. Materials and Methods
2.1. Protocol and Registration. The PRISMA Statement for
Reporting Systematic Reviews and Meta-Analyses of Studies
that Evaluate Health Care Interventions: Explanation and
Elaboration was utilized as a framework for this systematic
review [15].
2.2. Eligibility Criteria. All manuscripts assessing the quantitative effect of gastric bypass, gastric banding, sleeve gastrectomy, and gastric plication on infertility in females with
PCOS published between 1 January 1974 and 20 March
2015 were considered eligible for inclusion in this systematic
review. Studies involving vertical banded gastroplasty and
biliopancreatic diversion were not included.
2.3. Information Sources and Search. Search databases,
PubMed, Embase from 1974 to 20 March 2015, and MEDLINE
and MEDLINE Non-Indexed Items, were searched using the
following keywords: polycystic ovary syndrome, infertility,
bariatric surgery, gastric bypass, laparoscopic, Roux-en-Y,
gastric band, sleeve gastrectomy, and gastric plication. Reference lists were also scanned for relevant manuscripts.
2.4. Study Selection. Studies identified were screened for
relevance and suitability by the two authors. Manuscripts
lacking quantitative data, those lacking in relevance to the
study question, and those relating to male fertility were
excluded.
2.5. Data Collection Process. Results and data were extracted
following analysis and critical review of the results section of
original manuscripts.
Journal of Obesity
2.6. Data Items
Participant Information. This included sample numbers, age,
body mass index, and basic demographics.
Surgical Procedure and Technique. This list included Roux-enY gastric bypass (RYGB), gastric band (GB), gastric plication
(GP), or sleeve gastrectomy (SG), open or laparoscopic.
Comparisons. Comparisons were done for epidemiological
studies identified.
Outcomes. Outcomes were conception rate, pregnancy, biochemical markers of fertility and PCOS, and menstrual
regularity.
Study Design. The type of study and level of evidence were
recorded.
2.7. Risk of Bias in Individual Studies. Each study was individually assessed for risk of bias giving particular attention to
funding sources, limitations of study, and conflicts of interest
declared in the discussion section.
2.8. Summary Measures. As the literature primarily is composed of epidemiological studies, the principle summary
measure is sample conception rates before and following
surgery in addition to/or other biochemical markers of
fertility and PCOS within the same sample.
2.9. Synthesis of Results. Results of studies have been summarized; however, quantitative data have not been combined in
analysis.
3. Results and Discussion
68 manuscripts were identified which met the search criteria.
Out of these, 6 were included in analysis as they were relevant
and contained quantitative data. 19 manuscripts, despite
being relevant, had no quantitative data. 43 manuscripts were
not relevant. The 6 manuscripts that were included in the
analysis and their results are summarized in Table 1.
Eid et al. [16] demonstrated that, after laparoscopic RYGB
(75 cm Roux limb), weight loss was associated with amelioration of PCOS-associated symptoms including resolution
of menstrual abnormalities in all patients and resolution
of hirsutism in 52% of patients. Surgery also resulted in
resolution of T2D and improvement in hypertension and
dyslipidaemia. Five patients who were unable to conceive
preoperatively were able to conceive without the use of
hormones postoperatively although the time interval after
surgery is not mentioned in this paper.
In a study by Jamal et al. [17], 20 patients with PCOS
were followed up after RYGB (75 cm Roux limb and 30 cm
biliopancreatic limb) for a mean postoperative follow-up of
46.7 months. Preoperatively, 50% of the patients with PCOS
were infertile, 85% had menstrual dysfunction, and 70% had
hirsutism. Following surgery-induced weight loss, menstrual
irregularities were corrected with return of regular cycles in
Journal of Obesity
3
Table 1: Comparison of existing studies about bariatric surgery and female fertility.
Eid et al.
SOARD 2005
[16]
Stroh et al.
Zentralbl
Chir 2008
(paper in
German,
abstract in
English)
[13]
Doblado
et al. Ferti
Steril 2010
[19]
Participants
24 women with
PCOS
3 females
with PCOS
2 females with
infertility
secondary to
PCOS (and to
male factor)
Interventions
Laparoscopic
RYGB
Laparoscopic
LAGB
RYGB and
gastric band,
respectively
Outcomes
measured
Study design
Mean follow-up
(months)
156 women
(67 had
radiological
features of
PCOS and 11
were infertile)
RYGB
Gastric
plication or
RYGB
Laparoscopic
SG
Retrospective
Not stated
Retrospective
104
Not stated
46.7 ± 35.3
12
Not stated
One patient
(33%)
conceived
postoperatively
Following
IVF/ICSI, both
women
became
pregnant and
had
uncomplicated
deliveries
100%
postoperative
conception
rate in
infertile
patients with
PCOS who
desired
pregnancy
10 women
(71%) out of
14 who were
infertile
preoperatively
became
pregnant
after one
year
postoperatively
4 patients
(36%)
conceived
without any
formal fertility
treatment
Out of 30
patients with
irregular
cycles
preoperatively,
14 (47%)
had regular
cycles by the
end of 1 year
postoperatively
Hirsutism and
radiological
evidence of
PCOS resolved
in 80%;
menstrual
dysfunction
improved in
100%; urinary
incontinence
resolved or
improved in
42%
Not stated
27.5 ± 16
Results –
other
10 women
with PCOS
and infertility
69
premenopausal
married
females
Hirsutism,
stress urinary
incontinence,
menstrual
dysfunction,
infertility
Conception
and pregnancy
Resolution of
T2D, decreased
number of
patients with
hypertension
and
hyperlipidemia,
improvement
of PCOSassociated
symptoms
George and Azeez
Obes Surg
2013
(abstract
only) [20]
Regularity of
menstruation
and
conception
rate
% EWL,
glucose
levels,
conception
rate
Results, fertility
Talebpour
Obes Surg 2011
(abstract
only) [18]
Pre- and
postsurgery
conception
rate,
weight loss,
hirsutism,
menstrual
dysfunction,
obesity
associated
comorbidities
Retrospective
Mean excess
weight loss,
presence of
hirsutism,
regular
menstruation,
conception rate
after surgery,
obesity
associated
comorbidities
Retrospective
5 women
(previously
infertile) who
wanted to
conceive were
able to do so
after surgery
without the use
of clomiphene
Jamal et al.
SOARD
2012 [17]
The 3
patients had a
% EWL of
49, 67, and
41%,
respectively,
with glucose
levels
normalized
postoperatively
82% of patients without the need for hormonal treatment.
Hirsutism completely resolved in 29% and 77.8% of those with
T2D that had complete remission. Of the 10 patients who did
not conceive before surgery, 4 no longer desired pregnancy
Improvement
of glycemic
control,
PCOSassociated
symptoms,
hypertension,
depression,
GERD, and
urinary
incontinence
with the remaining 6 patients becoming pregnant within 3
years of surgery (5 of whom conceived without any hormonal
treatment). These patients did not develop any pregnancy
induced or postpartum complications.
4
In a case series of 5 patients who underwent IVF after
bariatric surgery, two women with infertility secondary
to PCOS and male infertility underwent RYGB and gastric banding, respectively [18]. Both conceived postoperatively following in vitro fertilization/intracytoplasmic sperm
insemination and had uncomplicated deliveries. This paper
suggests that although IVF appears to be safe after bariatric
surgery, ovarian hyperstimulation may present with features
similar to complications after weight loss surgery (especially
internal herniation after RYGB) and a high index of suspicion
is thus required.
Stroh et al. [13] described the progress of 3 patients who
underwent gastric banding. One of these patients conceived
postoperatively. Talebpour reported that gastric plication and
gastric bypass appear to have a positive effect on fertility in
an abstract presented at IFSO 2011 [18]. 10 women (71%) out
of 14 who were infertile preoperatively became pregnant one
year postoperatively. Out of 87 premenopausal patients who
had irregular menstrual cycles preoperatively, 70 (80%) had
regular cycles by the end of the first year postoperatively [18].
This work, only published in abstract form, does not compare
the effects of the two operations.
In another abstract presented by George and Azeez at
IFSO 2013 [20], 156 female patients between the ages of 20 and
50 underwent laparoscopic sleeve gastrectomy (SG) and were
followed up 6-monthly. Postoperatively, hirsutism resolved in
77 out of 96 patients (80%) and 54 out of 67 showed resolution
of radiological evidence of PCOS. 132 patients had menstrual
irregularities before surgery but all of these returned to a
normal menstrual pattern after SG. Four out of the 11 patients
who were unsuccessfully treated for infertility preoperatively
became pregnant postoperatively. This abstract also showed
that urinary stress incontinence resolved or substantially
improved in over 40% of patients. Unfortunately, this work
was only published as an abstract and there is no information
regarding the mean follow-up period, the preoperative BMIs,
and the nature of the study.
Dixon and O’Brien [21] found that 2 infertile patients
in their cohort became pregnant after laparoscopic gastric
banding. Unfortunately, the paper does not make the denominator clear and it is not possible to ascertain how many of
the 28 women with primary or secondary infertility were
followed up 1 year postoperatively. This paper was therefore
not included in the analysis table.
All these studies were very heterogeneous and had small
numbers of patients. It was thereby decided that any statistical
comparison of these studies would be futile. The definition
of infertility, the age of the patients, and the operations were
different. These could have important effects on postoperative
fertility and conception. Controls were not present in the
considered papers with patients being control of themselves
before and after bariatric surgery. It was difficult to carry
out analysis for bias in studies that were only presented as
conference abstracts. Another bias deals with one of the
analyzed studies that considered in vitro fertilization (often
performed for the male factor), while the others considered
spontaneous pregnancy.
Women of childbearing age form a significant percentage of patients being referred for and undergoing bariatric
Journal of Obesity
surgery. A review of admission data from more than 1,000
US hospitals between 1998 and 2005 revealed that almost
half of all patients undergoing inpatient surgical weight loss
procedures were women between the ages of 18 and 45 [22].
PCOS is very common in this patient group. A recent metaanalysis has shown that PCOS decreases significantly after
bariatric surgery from 45.6% preoperatively to 6.8% at 1 year
postoperatively [14].
The reproductive health of female participants was
investigated as part of the Longitudinal Assessment of
Bariatric Surgery (LABS-2) study with a self-administered
survey within 30 days preoperatively [23]. 1,538 females
were included and 13% of them had been diagnosed with
PCOS preoperatively. 42% of women who tried to become
pregnant preoperatively in this cohort of patients experienced
infertility (defined as 12 months of regular intercourse with
a man without contraception but no resulting pregnancy).
65% of these patients however had at least 1 pregnancy after
experiencing a period of infertility. A high rate of stillbirths
was self-reported by these women with the rate being twice
that expected in the USA (13.2 versus 6.2 per 1000 live births).
Future pregnancies (in the postoperative period) were an
important consideration to 30% of patients who were aged
18–44 and who did not report natural/surgical menopause,
hysterectomy, endometrial ablation, or sterilization (personal
or partner). This study revealed that women who were obese
by the age of 18 were more likely to report PCOS (14.4% versus
5%) and infertility (56% versus 25%) and less likely to have
ever been pregnant (75% versus 92%), compared with women
whose obesity started after the age of 30. Obesity at a young
age may be considered an indication for bariatric surgery in
effort to prevent infertility developing in later life. The LABS2 study is yet to report the postoperative reproductive health
results in this cohort of women.
PCOS in obese patients primarily manifests itself with
irregular or infrequent menstrual bleeding/amenorrhea, hirsutism, and infertility. It is thought that a 5% weight loss can
result in resolution of obesity-related anovulation; however,
there is little evidence that this is sufficient in morbidly obese
patients [24]. In a retrospective survey, 50% of women (98
patients) aged 40 years or younger with intact uterus and
ovaries had anovulatory cycles, defined as cycles of >35 days
longer, prior to bariatric surgery [22]. Of these 98 patients, 70
patients (71%) had a return of normal menstrual cycles after
surgery. Patients who regained ovulation postoperatively had
statistically significant greater weight loss compared to those
who remained anovulatory. Patients who had normal cycles
preoperatively still had normal menstrual cycles postoperatively despite the weight loss.
In a prospective study of 14 females with PCOS, amelioration in clinical symptoms was associated with significant improvements in testosterone, fasting glucose, cholesterol, insulin, and triglyceride levels at 6 and 12 months
after RYGB when compared to baseline [25]. Improvements
in biomarkers, hirsutism, and regularity of the menstrual
cycles did not correlate with the degree of weight change
in this study. Escobar-Morreale et al. also showed similar
improvements in total and free testosterone and amelioration
of insulin resistance estimated in a prospective study of 12
Journal of Obesity
premenopausal women with PCOS who underwent either
RYGB or biliopancreatic diversion [26].
Traditionally, bariatric surgery has been reserved for
patients with a body mass index (BMI) >40 kg/m2 or with
BMI >35 kg/m2 and one or more significant comorbid
conditions, when nonsurgical methods of weight loss have
failed. Recently, the National Institute for Health and Care
Excellence (NICE) in the UK suggested lowering the BMI
down to 30 kg/m2 in patients with a recent diagnosis of
T2D [27]. Infertility due to anovulation and PCOS amongst
morbidly obese women could potentially be viewed as an
additional indication for bariatric surgery. Although most
studies show amelioration of PCOS postoperatively, to date,
the number of studies showing improved fertility is small and
they mainly consist of retrospective analysis of small cohorts
of patients. As females of childbearing age make up a large
percentage of patients undergoing surgery, more research
is required in this area of metabolic and bariatric surgery
to enable clinicians to advise these women regarding their
reproductive health and fertility after surgery. Careful followup of these patients is required, as pregnancy is usually not
advised in the first 12–18 months postoperatively.
4. Conclusion
Bariatric surgery results in improvement of menstrual irregularities and hirsutism and amelioration of the metabolic
profile. Observational studies suggest that female fertility
improves following bariatric procedures and weight loss.
However, at this stage, it is difficult to recommend the
lowering of BMI criteria for patients with primary infertility
and PCOS and larger studies are required to confirm the
effects of bariatric surgery on fertility and to determine
whether different bariatric operations have different results
compared to nonsurgical methods of weight loss.
5
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
Conclusions
(i) Polycystic ovary syndrome (PCOS) is the most frequent cause of female infertility.
(ii) PCOS, hirsutism, and menstrual irregularities
improve after bariatric surgery.
(iii) The evidence for improvement in fertility after
bariatric surgery is still limited.
(iv) More studies are required to understand which operation (if any) would be best for this cohort of young
infertile women.
Competing Interests
[11]
[12]
[13]
[14]
The authors have no commercial associations that might be a
conflict of interests in relation to this article.
[15]
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Journal of Obesity