International evidence-based guideline

for the assessment and management of

polycystic
ovary syndrome 2018
Bariatric surgery In women with PCOS

• What is the effectiveness of lifestyle interventions compared to bariatric surgery

for improving fertility and adverse outcomes?
• Justification Bariatric surgery improves weight loss and can improve
comorbidities associated with PCOS. However, evidence in relation to fertility and
pregnancy outcomes is limited, with some concerns about potential perinatal
adverse effects of bariatric surgery. Given the concerns about the potential
perinatal adverse effects of bariatric surgery and the remaining controversies, no
recommendation can be made at this time about the use of bariatric surgery to
improve fertility and pregnancy outcomes in women with PCOS.
In-vitro fertilisation In women with PCOS
• The GDG deemed IVF should be considered after failed ovulation
induction treatment with high pregnancy rates per cycle, especially in
younger women. Given the risks and the high costs that can be
prohibitive for many patients, IVF should be considered third line
medical therapy. It was noted that conception and delivery are highly
valued by health professionals and women with PCOS and even when
cost and risks are increased, many may elect to undertake IVF. Health
Professionals must weigh benefits and risk when advising PCOS
patients to enable an informed decision.
5.9b Gonadotropin releasing hormone protocol

• In women with PCOS undergoing IVF/ICSI treatment, is the

gonadotropin releasing hormone antagonist protocol or gonadotropin
releasing hormone agonist long protocol the most effective for
improving fertility outcomes?
• The duration of stimulation with a GnRH antagonist approach is
around a day shorter than the standard ‘long-down regulation’
approach with a GnRH agonist. The rate of OHSS appears less with a
GnRH antagonist approach in comparison to the standard ‘long-down
regulation’ approach with a GnRH agonis
5.9c Trigger type
• In women with PCOS undergoing GnRH antagonist IVF/ICSI treatment,
is the use of hCG trigger or GnRH agonist trigger the most effective
for improving fertility outcomes?
• The choice to trigger final oocyte maturation with GnRH-agonist
instead of hCG is important in prevention of OHSS as hCG alone
induces oocyte maturation but is associated with OHSS. GnRH-
agonist triggers are associated with lower pregnancy rates, primarily
in fresh embryo transfers, which can be overcome in frozen cycles
Choice of FSH
• In women with PCOS undergoing (controlled) ovarian (hyper) stimulation
for IVF/ICSI, does the choice of FSH effect fertility outcomes?
• Only one small study in PCOS has been identified investigating uFSH versus
rFSH in PCOS during ovarian stimulation for IVF/ICSI [578]. This study shows
similar results to a systematic review and meta-analysis in the general IVF
population, where extensive research has concluded no significant
difference in birth rate or OHSS was detected and no further research in
the general population was recommended. Hence clinical choice of
gonadotrophin should depend on availability, convenience and costs.
Exogenous luteinizing hormone (LH)
• In women with PCOS undergoing (controlled) ovarian (hyper)
stimulation for IVF/ICSI, is exogenous LH treatment during IVF ± ICSI
effective for improving fertility outcome?
• There is no anticipated effect or benefit to add exogenous LH
supplement in women with PCOS undergoing ovarian stimulation for
IVF ± ICSI. There is insufficient evidence to determine the benefits of
using or not using exogenous LH.
Adjunct metformin
• In women with PCOS undergoing (controlled) ovarian (hyper) stimulation
for IVF ± ICSI, is adjunct metformin effective for improving fertility
outcomes?
• Women and health professionals would generally value an increased
clinical pregnancy rate (with no evidence of a difference in miscarriage
rate) and reduced OHSS (with its associated morbidity and rarely
mortality). Gastrointestinal side effects were recognised, but noted as mild
and self-limiting and may be minimised with lower metformin starting dose
and extended release preparations. Metformin was noted to be low cost
and readily available, and while off label use was generally allowed,
explanation is required for use.
In-vitro maturation
• In women with PCOS, is in-vitro maturation (IVM) effective for improving
fertility outcomes?
• The GDG deemed that key elements to consider with IVM included; a clear
definition of the term IVM, use in clinical units with sufficient expertise and
advantages of reduced risk of OHSS. The group considered the lack of
evidence as important. It was considered that IVM could be offered to
achieve pregnancy and live birth rates that may approach those of standard
IVF ± ICSI treatment, where frozen embryos are used. Given the lack of
evidence the group voted for a conditional consensus recommendation
that neither favoured this option or other options (IVF), with strong
research recommendations
Guideline development methods
• The International evidence–based guideline for the assessment and
management of PCOS underpins an international initiative to engage
women affected by PCOS and their health professionals to improve
health outcomes
Guideline development methods
• In the development of this guideline, we have sought not only to
inform or consult with women affected by PCOS, but to partner with
and empower women with PCOS, who are the ultimate beneficiaries
of this work. We have engaged with international consumer bodies in
PCOS and infertility to this end. This included Polycystic Ovary
Syndrome Association Australia (POSAA) (Australia), Verity (United
Kingdom), PCOS Challenge (United States), RESOLVE: The National
Fertility Association (United States), and Victorian Assisted
Reproductive Treatment Authority (VARTA) (Australia), who were
actively engaged throughout the guideline process.
Guideline development methods
• Clinical question development and prioritization
• An International survey and Delphi exercise was conducted to
develop and prioritise clinical questions to be addressed. A further
prioritisation exercise was conducted within the topic specific GDGs
and consumer advisory groups to rank the importance of clinical
questions to guide the evidence team and to reach consensus on
which clinical questions were to be addressed by a systematic review
or by narrative review.
Guideline development methods
• GDG – 1 Screening, diagnostic assessment, risk assessment and life-
stage
• GDG 2 - Prevalence, screening, diagnostic assessment and
management of emotional wellbeing
• GDG 3 – Lifestyle management and models of care
• GDG 4 – Medical treatment
• GDG 5 – Screening, diagnostic assessment and management of
infertility
Guideline development methods

• Outcome prioritisation using the GRADE method

• The most relevant outcomes were prioritised by ranking their
importance by health professionals and consumers to help resolve or
clarify disagreements and assist with grading the
evidence. The importance of outcomes may vary across cultures and
from different perspectives e.g. patients, public, health professionals
or policy-makers
Guideline development methods
• Adaptation of existing evidence-based guidelines
• Here we have updated and expanded the scope and evidence contained in the
2011 Australian guideline and, where appropriate methods have been applied,
integrated the WHO guideline.
• Evidence reviews to answer the clinical questions
• The links between the body of evidence, the clinical need for the question and
the clinical impact of the resulting recommendation(s), including potential
changes in usual care and the way care is organised, acceptability, feasibility and
resource implications are clearly explained in the accompanying GRADE evidence
to decision framework supporting the recommendation.
Inclusion of studies

• To determine the literature to be assessed further, a reviewer scanned the titles,

abstracts and keywords of every record retrieved by the search strategy. Studies
were selected by one reviewer in consultation with colleagues, using the PICO
selection criteria established a priori.
• Appraisal of the methodological quality/risk of bias of the evidence
• Methodological quality of the included studies was assessed using criteria
developed a priori according to study design. Individual quality items were
investigated using a descriptive component approach. Any disagreement or
uncertainty was resolved by discussion among the GDG to reach a consensus.