Polycystic Ovary Syndrome (PCOS) is associated with increased
risk of late but not early pregnancy loss after IVF
Adam H Balen,
Leeds Teaching Hospitals, UK
Polycystic Ovary Syndrome (PCOS) is the commonest cause of subfertility,
although IVF should be the treatment “of last resort” after lifestyle
modification and ovulation induction (Balen, et al Human
Reproduction Update 2016; 22: 687-708). There are a number of PCOS
phenotypes and associated endocrine and metabolic disturbances, which in
turn vary across ethnicities (Teede et al Fertil Steril 2018;110 : 364-379). Whilst PCOS is associated with increased risk of
miscarriage and pregnancy complications, the question is whether this is
secondary to PCOS itself, associated comorbidities or the mode of
conception.
A study of metabolic complications of pregnancy in 14,882 PCOS women
compared with 9,081,906 controls found women with PCOS to be more obese
(22.3% vs. 3.5%, P<0.001), with pre-gestational diabetes
(4.1% vs. 0.9%, p<0.001) and chronic hypertension (8.4% vs.
1.8%, P<0.001). Those with PCOS were more likely to develop
gestational diabetes, pregnancy associated hypertension and
pre-eclampsia (Mills et al, Human Reproduction 2020; 35 :
1666–1674).
The current study from China (He et al, BJOG xxxx ) assessed
pregnancy outcomes in 21,820 women who conceived after IVF, of whom
2,357 (10.8%) had PCOS. After adjustment for age and other confounders
the rate of early pregnancy loss (EPL), prior to 13 weeks, was not
associated with PCOS (16.6% versus 18.3%, OR 0.89, 95%CI, 0.79-0.99,P =.04). Whereas those with PCOS demonstrated a higher rate of
late pregnancy loss (LPL) (6.4% vs 3.6%, OR 1.81, 95% CI, 1.48-2.21,P <.001). In particular overweight and obese PCOS women
had higher odds of LPL (OR, 2.18; 95% CI, 1.48-3.21 and OR, 2.68; 95%
CI, 1.47–4.90) compared with normal weight women.
As might be expected women with PCOS were more likely to be overweight
and obese than those without PCOS (32.4% vs 16.1%, and 7.4% vs 2.2%,P <.001) and had higher rates of hypertensive disease
and diabetes mellitus (5.9% vs 1.2% and 2.7% vs 0.2%). Regardless of
gestational age and PCOS status, the odds of having a pregnancy loss was
higher in all women with an elevated BMI, especially in the second
trimester.
It is important to consider the distinction between natural and assisted
conception, and also the different aetiologies for early and late
pregnancy loss, with this study indicating an elevated BMI and
comorbidities in the PCOS women leading to an increased risk of LPL. A
number of studies have also identified an interaction between ethnicity,
PCOS phenotype and reproductive outcomes, and so this study of
predominantly Chinese women may not be representative of all women with
PCOS.
Lifestyle modification and health optimisation prior to pregnancy and
fertility treatment is of paramount importance for all women both to
reduce any risks during pregnancy and improve the long-term outcome for
the baby. This study reinforces the additional risks for women with
PCOS, which may be largely but not exclusively attributable to being
overweight. The approach should ideally be long-term and sustained, as
“quick fix” weight loss programmes are unlikely to substantially alter
the ability to achieve a successful pregnancy through IVF (Norman & MolFertil Steril 2018; 110 : 581-586).
Disclosure of interest: Dr. Balen reports personal fees from
Genesis Health Care LLP; Leeds Fertility; personal fees from Balance
Reproductive Health Ltd.; non-financial support from WHO GDG;
non-financial support from RCOG Council; non-financial support from
British Fertility Society; non-financial support from Lecturing –
widely; non-financial support from Medical advisor to Verity;
non-financial support from CRE-PCOS; non-financial support from FIGO,
outside the submitted work.
A completed disclosure of interest form is available to view online as
supporting information.