Müllerian-Inhibiting Substance/Anti-Müllerian Hormone as a Predictor of Preterm Birth in Polycystic Ovary Syndrome

Abstract Objective To consolidate evidence from systematic reviews and meta-analyses investigating the association between reproductive factors in women of reproductive age and their subsequent risk of cardiovascular disease. Design Umbrella review. Data sources Medline, Embase, and Cochrane databases for systematic reviews and meta-analyses from inception until 31 August 2019. Review methods Two independent reviewers undertook screening, data extraction, and quality appraisal. The population was women of reproductive age. Exposures were fertility related factors and adverse pregnancy outcomes. Outcome was cardiovascular diseases in women, including ischaemic heart disease, heart failure, peripheral arterial disease, and stroke. Results 32 reviews were included, evaluating multiple risk factors over an average follow-up period of 7-10 years. All except three reviews were of moderate quality. A narrative evidence synthesis with forest plots and tabular presentations was performed. Associations for composite cardiovascular disease were: twofold for pre-eclampsia, stillbirth, and preterm birth; 1.5-1.9-fold for gestational hypertension, placental abruption, gestational diabetes, and premature ovarian insufficiency; and less than 1.5-fold for early menarche, polycystic ovary syndrome, ever parity, and early menopause. A longer length of breastfeeding was associated with a reduced risk of cardiovascular disease. The associations for ischaemic heart disease were twofold or greater for pre-eclampsia, recurrent pre-eclampsia, gestational diabetes, and preterm birth; 1.5-1.9-fold for current use of combined oral contraceptives (oestrogen and progesterone), recurrent miscarriage, premature ovarian insufficiency, and early menopause; and less than 1.5-fold for miscarriage, polycystic ovary syndrome, and menopausal symptoms. For stroke outcomes, the associations were twofold or more for current use of any oral contraceptive (combined oral contraceptives or progesterone only pill), pre-eclampsia, and recurrent pre-eclampsia; 1.5-1.9-fold for current use of combined oral contraceptives, gestational diabetes, and preterm birth; and less than 1.5-fold for polycystic ovary syndrome. The association for heart failure was fourfold for pre-eclampsia. No association was found between cardiovascular disease outcomes and current use of progesterone only contraceptives, use of non-oral hormonal contraceptive agents, or fertility treatment. Conclusions From menarche to menopause, reproductive factors were associated with cardiovascular disease in women. In this review, presenting absolute numbers on the scale of the problem was not feasible; however, if these associations are causal, they could account for a large proportion of unexplained risk of cardiovascular disease in women, and the risk might be modifiable. Identifying reproductive risk factors at an early stage in the life of women might facilitate the initiation of strategies to modify potential risks. Policy makers should consider incorporating reproductive risk factors as part of the assessment of cardiovascular risk in clinical guidelines. Systematic review registration PROSPERO CRD42019120076.

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Polycystic ovary syndrome and extremely preterm birth: A nationwide register-based study

PLoS ONE ◽

10.1371/journal.pone.0246743 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0246743

Author(s):

Heiddis Valgeirsdottir ◽

Inger Sundström Poromaa ◽

Theodora Kunovac Kallak ◽

Eszter Vanky ◽

Tansim Akhter ◽

...

Keyword(s):

Preterm Birth ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Multinomial Logistic Regression ◽

Future Research ◽

Ovary Syndrome ◽

Increased Risk ◽

Extremely Preterm ◽

Spontaneous Onset ◽

Extremely Preterm Birth

Introduction Women with polycystic ovary syndrome (PCOS) have increased risk of pregnancy complications, including preterm birth before 37 weeks. However, if this increased risk also includes extremely preterm births (<28 weeks) is unknown. Such information is important to identify women at risk and tailor antenatal care, since child morbidity and mortality become more prevalent with increasing prematurity. Aims To investigate the association between PCOS and extremely preterm birth, and whether onset of PCOS-related preterm birth is predominantly spontaneous or medically indicated. Material and methods This was a nationwide register-based cohort study in Sweden. The study population was all live singleton births registered in the Swedish Medical Birth Register 2005–2014 (n = 1 046 448). Women with and without PCOS were compared by severity of preterm birth [extremely (22+0 to 27+6 weeks), very (28+0 to 31+6 weeks) and moderately (32+0 to 36+6 weeks)] and delivery onset mode (spontaneous or medically indicated). Multinomial logistic regression was performed to estimate adjusted odds ratios (aOR) with 95% confidence intervals (CI). Adjustments were made for maternal age, parity, body mass index, smoking, country of birth and year of delivery. Results During the study period, 1.3% of the women giving birth had PCOS diagnosis. They had an overall higher preterm birth rate than women without PCOS (6.7% and 4.8%, respectively). Women with PCOS had increased odds of preterm birth of all severities, with the highest odds for extremely preterm birth (aOR 2.3; 95% CI 1.7–3.0), particularly of spontaneous onset (aOR 2.7; 95% CI 2.0–3.6). Conclusions Women with PCOS had more than a two-fold increased risk of extremely preterm birth with spontaneous onset than women without such diagnosis. This can be important in antenatal risk assessment of preterm birth in women with PCOS. Future research is warranted to investigate the biological mechanisms behind preterm birth in women with PCOS.

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