Is it time to screen for cardiometabolic risk factors prior to
ART?
Catherine Nelson-Piercy
Guy’s & St Thomas’ Foundation Trust
London
Email: catherine.nelson-piercy@gstt.nhs.uk
Coronary heart disease kills twice as many women as breast cancer in the
UK and is the single biggest killer of women worldwide. Underlying risk
factors include hypertension, diabetes, hyperlipidaemia, obesity and
smoking. Mulder and colleagues have performed a systematic review and
meta-analysis of the literature and demonstrated that women with
infertility are significantly more likely to have certain
cardiometabolic risk factors, namely increased BMI, cholesterol and
triglycerides, when compared with fertile women (BJOG 2020 xxxx). The
differences are small; cholesterol 18.13 mg/dl (0.47 mmol/l) higher,
triglycerides 43.75 mg/dl (0.49 mmol/l) higher and BMI 0.78
kg/m2 higher.
It is perhaps not surprising that in a subset of infertile women with
polycystic ovarian syndrome (PCOS) total cholesterol, fasting glucose
and fasting insulin were increased and HDL cholesterol decreased
compared to fertile women. PCOS is established as a condition commonly
associated with obesity, impaired glucose tolerance with insulin
resistance and dyslipidaemia. But the finding that this adverse
metabolic milieu extends to women with other causes of infertility is
novel and has important implications for the screening and counselling
of women undergoing assisted reproductive techniques (ART).
Even if only singleton pregnancies are considered and confounders such
as maternal age controlled for, there is a well-documented association
between in vitro fertilization (IVF) / ART and an increased risk of both
maternal and perinatal adverse outcomes. Resulting pregnancies are
significantly more likely to be complicated by pregnancy-induced
hypertension, gestational diabetes mellitus (GDM), preterm birth, low
birth weight and perinatal mortality [Palomba et al. Reprod Biol
Endocrinol 2016;14(1):1–25]. The pre-existing, mild, metabolic
derangement described by Mulder et al. provides one explanation for
these associations. Pre-eclampsia, particularly if recurrent, preterm
and associated with growth restricted infants, is associated with
increased risk of subsequent cardiovascular disease [Brouwers et al
BJOG 2018 125 (13), 1642-1654]. Women with infertility are more likely
to be overweight, have dyslipidaemia predisposing them to pre-eclampsia,
small babies, preterm delivery and cardiovascular disease.
Cardiovascular disease is the leading cause of maternal mortality in the
UK, Australia and USA. Most women who die from heart disease in
pregnancy are not aware of their underlying cardiac disease
prepregnancy. Several women who died from heart disease during or after
pregnancy following ART had cardiovascular risk factors but no
assessment had been made of their cardiovascular health status prior to
ART [Knight et al. NPEU 2019.
https://www.npeu.ox.ac.uk/mbrrace-uk/reports]. Parikh and coworkers
found an increased risk of coronary heart disease, stroke or heart
failure in women with infertility compared to fertile women [Parikh et
al. Human Repro 2012;27(2):568–75]. Dutch workers have demonstrated
that in obese infertile women a six month lifestyle intervention reduced
BMI and metabolic syndrome prior to ART [van Dammen et al. PLoS one
2018 13(1): e0190662].
What do these findings mean for fertility services? Pre-pregnancy
counselling to advise women regarding life-style changes; specifically
to stop smoking, reduce BMI, and dietary modification to improve
dyslipidaemia, may not only reduce the risk of GDM, pre-eclampsia and
other adverse pregnancy outcomes in women receiving ART, but also
potentially reduce cardiac events in pregnancy, postpartum and later in
that woman’s life. Fertility units are uniquely placed to provide, and
should seize the opportunity to offer, at least minimum screening for
these women with blood pressure measurement, urinalysis, blood glucose,
and fasting lipids. Moreover MBRRACE recommended that ‘women with
cardiac risk factors should have a cardiac assessment prior to receiving
ART’ [Knight et al. NPEU 2019].
No disclosures. A completed disclosure of interest form is
available to view online as supporting information.
Acknowledgements. Many thanks to Professors Peter Braude and
Marian Knight for their constructive comments.