- 1Leeds Centre for Reproductive Medicine, Leeds Teaching Hospitals, Leeds LS14 6UH, UK a.balen@nhs.net.
- 2Leeds Centre for Reproductive Medicine, Leeds Teaching Hospitals, Leeds LS14 6UH, UK.
- 3Monash
Centre for Health Research and Implementation, School of Public Health
and Preventive Medicine, Monash University, Monash Medical Centre, 43-51
Kanooka Grove, Clayton, VIC 3168, Australia.
- 4Institute of Reproductive & Developmental Biology, Hammersmith Hospital, London, UK.
- 5Penn State College of Medicine, 500 University Drive, H103, Hershey, PA 17033, USA.
- 6Faculty of Medicine, University of Colombo, PO Box 271, Kynsey Road, Colombo 008, Sri Lanka.
- 7Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
- 8Department of Reproductive Medicine & Gynaecology, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
- 9The Robinson Institute, University of Adelaide, Norwich House, 55 King William Street, North Adelaide, SA 5005, Australia.
Abstract
BACKGROUND:
Here
we describe the consensus guideline methodology, summarise the
evidence-based recommendations we provided to the World Health
Organisation (WHO) for their consideration in the development of global
guidance and present a narrative review on the management of anovulatory
infertility in women with polycystic ovary syndrome (PCOS).
OBJECTIVE AND RATIONALE:
The aim of this paper was to present an evidence base for the management of anovulatory PCOS.
SEARCH METHODS:
The
evidence to support providing recommendations involved a collaborative
process for: (i) identification of priority questions and critical
outcomes, (ii) retrieval of up-to-date evidence and exiting guidelines,
(iii) assessment and synthesis of the evidence and (iv) the formulation
of draft recommendations to be used for reaching consensus with a wide
range of global stakeholders. For each draft recommendation, the
methodologist evaluated the quality of the supporting evidence that was
then graded as very low, low, moderate or high for consideration during
consensus.
OUTCOMES:
Evidence
was synthesized and we made recommendations across the definition of
PCOS including hyperandrogenism, menstrual cycle regulation and ovarian
assessment. Metabolic features and the impact of ethnicity were covered.
Management includes lifestyle changes, bariatric surgery,
pharmacotherapy (including clomiphene citrate (CC), aromatase
inhibitors, metformin and gonadotropins), as well as laparoscopic
surgery. In-vitro fertilization (IVF) was considered as were the risks
of ovulation induction and of pregnancy in PCOS. Approximately 80% of
women who suffer from anovulatory infertility have PCOS. Lifestyle
intervention is recommended first in women who are obese largely on the
basis of general health benefits. Bariatric surgery can be considered
where the body mass index (BMI) is ≥35 kg/m2 and lifestyle
therapy has failed. Carefully conducted and monitored pharmacological
ovulation induction can achieve good cumulative pregnancy rates and
multiple pregnancy rates can be minimized with adherence to recommended
protocols. CC should be first-line pharmacotherapy for ovulation
induction and letrozole can also be used as first-line therapy.
Metformin alone has limited benefits in improving live birth rates.
Gonadotropins and laparoscopic surgery can be used as second-line
treatment. There is no clear evidence for efficacy of acupuncture or herbal
mixtures in women with PCOS. For women with PCOS who fail lifestyle and
ovulation induction therapy or have additional infertility factors, IVF
can be used with the safer gonadotropin releasing hormone (GnRH)
antagonist protocol. If a GnRH-agonist protocol is used, metformin as an
adjunct may reduce the risk of ovarian hyperstimulation syndrome.
Patients should be informed of the potential side effects of ovulation
induction agents and of IVF on the foetus, and of the risks of multiple
pregnancy. Increased risks for the mother during pregnancy and for the
child, including the exacerbating impact of obesity on adverse outcomes,
should also be discussed.
WIDER IMPLICATIONS:
This
guidance generation and evidence-synthesis analysis has been conducted
in a manner to be considered for global applicability for the safe
administration of ovulation induction for anovulatory women with PCOS.
©
The Author 2016. Published by Oxford University Press on behalf of the
European Society of Human Reproduction and Embryology. All rights
reserved. For Permissions, please email: journals.permissions@oup.com.
KEYWORDS:
anovulatory
infertility; aromatase inhibitors; clomiphene citrate; gonadotropin
therapy; laparoscopic ovarian diathermy; lifestyle; metformin; ovulation
induction; polycystic ovary syndrome (PCOS); weight management
