Literature DB >> 21998337

Risk of adverse pregnancy outcomes in women with polycystic ovary syndrome: population based cohort study.

Nathalie Roos1, Helle Kieler, Lena Sahlin, Gunvor Ekman-Ordeberg, Henrik Falconer, Olof Stephansson.   

Abstract

OBJECTIVE: To study the risk of adverse pregnancy outcomes in women with polycystic ovary syndrome, taking into account maternal characteristics and assisted reproductive technology.
DESIGN: Population based cohort study.
SETTING: Singleton births registered in the Swedish medical birth register between 1995 and 2007. PARTICIPANTS: By linkage with the Swedish patient register, 3787 births among women with a diagnosis of polycystic ovary syndrome and 1,191,336 births among women without such a diagnosis. MAIN OUTCOME MEASURES: Risk of adverse pregnancy outcomes (gestational diabetes, pre-eclampsia, preterm birth, stillbirth, neonatal death, low Apgar score (<7 at five minutes), meconium aspiration, large for gestational age, macrosomia, small for gestational age), adjusted for maternal characteristics (body mass index, age), socioeconomic factors (educational level, and cohabitating with infant's father), and assisted reproductive technology.
RESULTS: Women with polycystic ovary syndrome were more often obese and more commonly used assisted reproductive technology than women without such a diagnosis (60.6% v 34.8% and 13.7% v 1.5%). Polycystic ovary syndrome was strongly associated with pre-eclampsia (adjusted odds ratio 1.45, 95% confidence interval 1.24 to 1.69) and very preterm birth (2.21, 1.69 to 2.90) and the risk of gestational diabetes was more than doubled (2.32, 1.88 to 2.88). Infants born to mothers with polycystic ovary syndrome were more prone to be large for gestational age (1.39, 1.19 to 1.62) and were at increased risk of meconium aspiration (2.02, 1.13 to 3.61) and having a low Apgar score (<7) at five minutes (1.41, 1.09 to 1.83).
CONCLUSIONS: Women with polycystic ovary syndrome are at increased risk of adverse pregnancy and birth outcomes that cannot be explained by assisted reproductive technology. These women may need increased surveillance during pregnancy and parturition.

Entities:  

Mesh:

Year:  2011        PMID: 21998337      PMCID: PMC3192872          DOI: 10.1136/bmj.d6309

Source DB:  PubMed          Journal:  BMJ        ISSN: 0959-8138


Introduction

Polycystic ovary syndrome is one of the most common endocrine disorders, affecting about 5-15% of women of reproductive age.1 2 3 The condition is characterised by oligo-ovulation or anovulation, biochemical or clinical hyperandrogenism, and polycystic ovaries. According to the Rotterdam consensus from 2003, the presence of two of three of these criteria fulfils a diagnosis of polycystic ovary syndrome.4 The cause of polycystic ovary syndrome is not fully understood, but evidence of a genetic component has been recognised in family and twin studies.5 Oligo-ovulation or anovulation in women with polycystic ovary syndrome is a major cause of infertility, and such women might require ovulation induction or assisted reproductive technology to become pregnant.6 Changes to lifestyle can, however, improve the metabolic and endocrine consequences of having polycystic ovary syndrome, thus possibly improving infertility caused by anovulation.7 Evidence suggests that polycystic ovary syndrome has a negative impact on pregnancy outcomes, with an increased risk of gestational diabetes, hypertensive disease during pregnancy, and preterm birth.8 Available studies are, however, limited in size and have mainly included women undergoing assisted reproductive technology.8 9 Consequently the extent to which the risk of adverse pregnancy outcomes in women with polycystic ovary syndrome is attributed to the underlying disorder or infertility treatment is uncertain. We carried out a large nationwide cohort study of pregnant women, including pregnancies conceived spontaneously and by assisted reproductive technology to evaluate the risks of adverse pregnancy and birth outcomes in women with polycystic ovary syndrome.

Methods

From the Swedish medical birth register we created a cohort among women with singleton pregnancies giving birth between 1995 and 2007. Women with polycystic ovary syndrome are more likely to undergo assisted reproductive technology, with its higher frequency of twins and higher multiple births. Because twin and multiple pregnancies differ in fetal growth and duration of gestation and have a higher occurrence of complications during pregnancy we excluded such pregnancies from the study population. Using the unique personal identification number assigned to each citizen at birth or immigration we linked data from the Swedish medical birth register with the Swedish patient and education registers.10 The Swedish patient register, established in 1964 (nationwide since 1987), includes information on dates of hospital admissions, discharges, and diagnoses classified according to ICD codes (international classification of diseases, 7-10th revisions). Since 2001 this registry has also included information on out-patient hospital visits. We recorded the date of the first diagnosis of polycystic ovary syndrome according to ICD codes: ICD-7, 275.20 and ICD-8, 256.90 (Stein-Leventhals syndrome); ICD-9, 256E; and ICD-10, E28.2. In the Swedish version of ICD-7 and ICD-8 the codes correspond to the formerly known Stein-Leventhals syndrome. For ICD-9 and ICD-10 the code is specified as polycystic ovary syndrome and Stein-Leventhals syndrome.

Register data

Data from the Swedish medical birth register include information on about 98% of births in Sweden, with information on the mother as well as the pregnancy, delivery, and neonatal period. Data are prospectively collected, starting at the woman’s first antenatal visit.11 We classified maternal age (years) at birth into four groups: 13-24, 25-29, 30-34, and ≥35. Body mass index was calculated (weight (kg)/(height (m)2) and the women categorised as lean (body mass index ≤19.9), normal weight (20.0-24.9), overweight (25.0-29.9), or obese (≥30.0). Parity was classified into nulliparous or parous women. Through linkage with the education register we obtained information on the number of years of formal education completed as of 1 January 2008, categorised as 11 or fewer or 12 or more. Cigarette smoking was recorded as none, 1-9 cigarettes daily, or 10 or more cigarettes daily. The Swedish medical birth register also contains information on whether the pregnancy was conceived by assisted reproductive technology or not and information on concurrent diseases such as diabetes mellitus and essential hypertension by checkbox as well as ICD-9 and ICD-10 codes. Pre-eclampsia was defined as a blood pressure reading of 140/90 mm Hg or more with proteinuria of more than 0.3 g over 24 hours. Gestational diabetes was, according to clinical practice, defined as plasma glucose levels of 12.2 mmol/L or more after oral glucose tolerance test (75 g glucose orally administered and plasma glucose measured after two hours) or fasting blood glucose levels of 7.0 mmol/L or more. Infants born small for gestational age were defined as having birth weights of less than 2 standard deviations below the mean for gestational age and sex of the infant. Similarly, large for gestational age was defined as a birth weight of more than 2 standard deviations above the mean for gestational age. Macrosomia was defined as a birth weight of 4500 g or more. Post-term pregnancy was defined as delivery at 42 weeks or more of gestation and preterm birth as delivery at less than 37 weeks of gestation, classified as moderately (32+0 to 36+6 weeks) and very preterm birth (<32 weeks). Stillbirth was defined as intrauterine fetal death after 28 weeks of gestation. A low Apgar score was defined as less than 7 at five minutes. Neonatal death was defined as death of the infant from 0 to 27 days after birth. The presence of meconium aspiration was obtained by diagnosis at discharge.

Statistical analysis

The main outcome measures were gestational diabetes, pre-eclampsia, preterm birth, stillbirth, neonatal death, low Apgar score, meconium aspiration, large for gestational age, macrosomia, and small for gestational age. Using logistic regression we estimated the risk of adverse pregnancy outcomes in relation to polycystic ovary syndrome by crude and adjusted odds ratios with 95% confidence intervals. Data were analysed using the SAS software version 9.2. We compared women with a diagnosis of polycystic ovary syndrome with women with no such diagnosis, taking into account possible confounders, such as maternal age, body mass index, parity, years of formal education, cigarette consumption, undergoing assisted reproductive technology, and calendar year of delivery. Absolute rates were standardised for difference in characteristics between women with and without polycystic ovary syndrome. In additional analyses we tested for residual confounding for the variables maternal age, body mass index, and parity by a finer categorisation and by analysing the continuous variables in a linear or linear-quadratic model. Assisted reproductive technology refers only to in vitro fertilisation including intracytoplasmic sperm injection and not other forms of assisted reproductive technology such as ovulation induction or insemination. Women tend to repeat pregnancy outcomes in successive births. Among women with polycystic ovary syndrome, 74.1% delivered one infant during the study period, 23.2% two infants, and 2.7% three or more infants. The corresponding frequencies among women without polycystic ovary syndrome were 53.0%, 38.1%, and 8.9%. Because observations are not independent in women who delivered more than once during the study period, we calculated estimates using clustered data in the generalised estimation equation method (PROC GENMOD). We used a formal interaction test in the logistic regression model to estimate the possible effect modification of assisted reproductive technology and body mass index on the association between polycystic ovary syndrome and preterm birth.

Results

A total of 1 195 123 singleton births between 1995 and 2007 were included in the cohort, with 3787 births among mothers with a diagnosis of polycystic ovary syndrome. Women with polycystic ovary syndrome were more likely to be nulliparous than women with no such diagnosis (53.0%, n=1990 v 43.8%, n=520 106, P<0.001). Undergoing assisted reproductive technology was more common in women with polycystic ovary syndrome (13.7%, n=510 v 1.5%, n=18 058, P<0.001). Women with polycystic ovary syndrome had an almost doubled prevalence of a body mass index greater than 25.0 (60.6%, n=1980 and 34.8%, n=348 340, P<0.001). Giving birth at advanced maternal age (>35 years) was more common in women with than without polycystic ovary syndrome (19.9%, n=753 and 17.6%, n=209 125, P<0.001). Women with polycystic ovary syndrome were more likely to have hypertensive disease and diabetes mellitus than women without polycystic ovary syndrome (table 1).
Table 1

 Characteristics of women with and without polycystic ovary syndrome (PCOS) giving birth to singleton pregnancies (1 195 123 total births) in Sweden, 1995 to 2007

Maternal characteristicsNo of births (rate %)P value*
Women with PCOS (n=3787)Women without PCOS (n=1 191 336)
Age (years):
 13-24339 (8.95)188 795 (15.85)<0.001
 25-29†1180 (31.16)390 088 (32.74)
 30-341515 (40.01)403 303 (33.85)
 ≥35753 (19.88)209 125 (17.55)
 Data missing025
Body mass index:
 ≤19.9148 (4.53)99 360 (9.91)<0.001
 20.0-24.9†1140 (34.88)554 456 (55.33)
 25.0-29.9932 (28.52)245 606 (24.51)
 ≥30.01048 (32.07)102 734 (10.25)
 Data missing519189 180
Parity:
 01990 (52.55)520 106 (43.66)<0.001
 ≥1†1797 (47.45)671 206 (56.34)
 Data missing024
Education level (years):
 ≤112139 (56.69)663 449 (56.11)0.47
 ≥12†1634 (43.31)518 974 (43.89)
 Data missing148913
Cigarette consumption (daily):
 None†3192 (90.42)988 375 (88.60)0.003
 1-9232 (6.57)87 909 (7.88)
 ≥10106 (3.00)39 291 (3.52)
 Data missing25775 761
Assisted reproductive technology:
 Yes515 (13.60)18 020 (1.51)<0.001
 No3272 (86.40)1 173 316 (98.49)
Essential hypertension:
 Yes26 (0.69)3345 (0.28)<0.001
 No3761 (99.31)1 187 991 (99.72)
Diabetes mellitus:
 Yes76 (2.01)4596 (0.38)<0.001
 No3711 (97.99)1 186 767 (99.62)

*Wald test of overall effect (test of general heterogeneity).

†Reference group.

Characteristics of women with and without polycystic ovary syndrome (PCOS) giving birth to singleton pregnancies (1 195 123 total births) in Sweden, 1995 to 2007 *Wald test of overall effect (test of general heterogeneity). †Reference group. Tables 2 and 3 present absolute rates, absolute risk differences standardised for the difference in characteristics between women with and without polycystic ovary syndrome, and crude and adjusted relative risks for adverse pregnancy and birth outcomes.
Table 2

 Pregnancy outcomes in women with and without polycystic ovary syndrome (PCOS) giving birth to singleton pregnancies (1 195 123 total births) in Sweden, 1995 to 2007

Pregnancy outcomesNo of births (rate %)Standardised absolute risk difference* (%) in women with PCOSCrude odds ratio† (95% CI)Adjusted odds ratio† (95% CI)P value
Women with PCOS (n=3787)Women without PCOS (n=1 191 336)
Gestational diabetes:
 Yes125 (3.30)10 672 (0.90)1.853.78 (3.16 to 4.52)2.32 (1.88 to 2.88)<0.001
 No3662 (96.70)1 180 664 (99.10)1.001.00
Pre-eclampsia:
 Yes221 (5.84)35 129 (2.95)1.742.04 (1.78 to 2.34)1.45 (1.24 to1.69)<0.001
 No3566 (94.16)1 156 207 (97.05)1.001.00
Antepartum bleeding or placental complications:
 Yes59 (1.56)14 490 (1.22)1.29 (0.99 to 1.66)1.14 (0.85 to 1.53)0.37
 No3728 (98.44)1 176 846 (98.78)1.001.00
Caesarean section‡:
 Yes846 (22.44)174 298 (14.68)2.751.69 (1.56 to 1.82)1.18 (1.07 to 1.29)0.001
 No2924 (77.56)1 013 112 (85.32)1.001.00
 Data missing030
Very preterm birth (<31+6 weeks)‡:
 Yes65 (1.73)7999 (0.67)0.942.59 (2.02 to 3.31)2.21 (1.69 to 2.90)<0.001
 No3701 (98.27)1 178 296 (99.33)1.001.00
 Data missing41145
Moderately preterm birth (32+0 to 36+6 weeks)‡§:
 Yes226 (6.11)50 352 (4.27)1.381.46 (1.28 to 1.67)1.31 (1.13 to 1.53)0.0004
 No3475 (93.89)1 127 944 (95.73)1.001.00
 Data missing41145
Post-term birth (>42+0 weeks)‡:
 Yes252 (6.69)86 771 (7.31)−1.390.91 (0.80 to 1.03)0.82 (0.71 to 0.95)0.0069
 No3514 (93.31)1 099 524 (92.69)1.001.00
 Data missing41145

*Estimated for significantly associated outcomes.

†Adjusted for maternal age, parity, body mass index, years of education, cigarette consumption, assisted reproductive technology, and year of delivery.

‡Live births only.

§Risk compared with deliveries at 37 weeks and later.

Table 3

 Perinatal outcomes in women with and without polycystic ovary syndrome (PCOS) giving birth to singleton pregnancies (1 195 123 total births) in Sweden, 1995 to 2007

Perinatal outcomesNo of births (rate %)Standardised absolute risk difference (%) in women with PCOS†Crude odds ratio* (95% CI)Adjusted odds ratio* (95% CI)P value
Women with PCOS (n=3787)Women without PCOS (n=1 191 336)
Stillbirth:
 Yes17 (0.45)3896 (0.33)1.38 (0.85 to 2.22)0.90 (0.50 to 1.63)0.73
 No3770 (99.55)1 187 440 (99.67)1.001.00
Apgar score <7 at 5 minutes‡:
 Yes71 (1.89)12 909 (1.10)0.541.74 (1.38 to 2.21)1.41 (1.09 to 1.83)0.0095
 No3680 (98.11)1 165 776 (98.90)1.001.00
Data missing198755
Neonatal death (0-27 days)‡:
 Yes11 (0.29)2179 (0.18)1.59 (0.88-´to 2.88)1.58 (0.81 to 3.07)0.18
 No3759 (99.71)1 185 261 (99.82)1.001.00
Meconium aspiration‡:
 Yes13 (0.34)1738 (0.15)0.172.36 (1.37 to 4.07)2.02 (1.13 to 3.61)0.018
 No3757 (99.66)1 185 702 (99.85)1.001.00
Large for gestational age:
 Yes238 (6.32)45 421 (3.84)1.691.69 (1.48 to 1.93)1.39 (1.19 to 1.62)<0.001
 No3526 (93.68)1 138 532 (96.69)1.001.00
Data missing237383
Macrosomia (birth weight ≥4500 g):
 Yes194 (5.14)47 937 (4.04)1.29 (1.11 to 1.49)1.16 (0.99 to 1.36)0.072
 No3582 (94.86)1 139 030 (95.96)1.001.00
 Data missing114369
Small for gestational age:
 Yes89 (2.36)27 192 (2.30)1.03 (0.84 to 1.27)1.01 (0.81 to 1.27)0.91
 No3675 (97.64)1 156 761 (97.70)1.001.00
 Data missing237383

*Adjusted for maternal age, parity, body mass index, years of education, cigarette consumption, assisted reproductive technology, and year of delivery.

†Estimated for significantly associated outcomes.

‡Live births only.

Pregnancy outcomes in women with and without polycystic ovary syndrome (PCOS) giving birth to singleton pregnancies (1 195 123 total births) in Sweden, 1995 to 2007 *Estimated for significantly associated outcomes. †Adjusted for maternal age, parity, body mass index, years of education, cigarette consumption, assisted reproductive technology, and year of delivery. ‡Live births only. §Risk compared with deliveries at 37 weeks and later. Perinatal outcomes in women with and without polycystic ovary syndrome (PCOS) giving birth to singleton pregnancies (1 195 123 total births) in Sweden, 1995 to 2007 *Adjusted for maternal age, parity, body mass index, years of education, cigarette consumption, assisted reproductive technology, and year of delivery. †Estimated for significantly associated outcomes. ‡Live births only. In the adjusted analysis, women with a previous diagnosis of polycystic ovary syndrome had a higher risk of developing gestational diabetes than women with no such diagnosis (adjusted odds ratio 2.32, 95% confidence interval 1.88 to 2.88), whereas the adjusted risk difference was 1.81%. There was also a strong association between polycystic ovary syndrome and pre-eclampsia (1.45, 1.24 to 1.69) and very preterm birth (2.21, 1.69 to 2.90). Women with polycystic ovary syndrome had an 18% higher risk of undergoing caesarean section (both emergency and elective) compared with women without polycystic ovary syndrome (table 2). Infants born to mothers with a previous diagnosis of polycystic ovary syndrome were more often large for gestational age (1.39, 1.19 to 1.62) and were also at increased risk of meconium aspiration (2.02, 1.13 to 3.61) and a low Apgar score at five minutes (1.41, 1.09 to 1.83). The risk of neonatal death was not significantly increased (1.58, 0.81 to 3.07; table 3). No residual confounding for maternal age, body mass index, and parity was found in sensitivity analyses (data not shown). In a stratified analysis the adjusted odds ratio for preterm birth (<37+0 weeks) among women with polycystic ovary syndrome undergoing assisted reproductive technology was 1.08 (95% confidence interval 0.76 to 1.53) and among women with polycystic ovary syndrome conceiving spontaneously was 1.58 (1.33 to 1.79) (P=0.055 for interaction, table 4). The interaction between body mass index and polycystic ovary syndrome and the association with preterm birth was not significant.
Table 4

 Adjusted odds ratios of women with and without polycystic ovary syndrome (PCOS) and singleton preterm births (<37+0 weeks) undergoing assisted reproductive technology in Sweden, 1995 to 2007

Preterm birthAssisted reproductive technology*RateAdjusted odds ratio† (95% CI)No assisted reproductive technology*RateAdjusted odds ratio† (95% CI)
Women with PCOSWomen without PCOSYesNo
Yes4114007.961.08 (0.76 to 1.53)25658 7237.831.54 (1.33 to 1.79)
No47416 6187.771.0030121 113 4265.011.00
Data missing241167

*P=0.055 for interaction analysis for assisted reproductive technology and PCOS in relation to preterm birth.

†Adjusted for maternal age, parity, body mass index, years of education, cigarette consumption, and assisted reproductive technology.

Adjusted odds ratios of women with and without polycystic ovary syndrome (PCOS) and singleton preterm births (<37+0 weeks) undergoing assisted reproductive technology in Sweden, 1995 to 2007 *P=0.055 for interaction analysis for assisted reproductive technology and PCOS in relation to preterm birth. †Adjusted for maternal age, parity, body mass index, years of education, cigarette consumption, and assisted reproductive technology.

Discussion

In the present population based study a diagnosis of polycystic ovary syndrome was associated with increased risks of adverse pregnancy outcomes that could not be attributed to the increased use of assisted reproductive technology or maternal characteristics such as advanced age or being overweight or obese.

Comparison with other studies

In previous studies preterm birth has been correlated to assisted reproductive technology, obesity, and polycystic ovary syndrome.8 12 13 This is in congruence with the findings of this study and furthermore we also found that the risk of preterm birth among women with polycystic ovary syndrome could not be explained by maternal characteristics such as advanced age, smoking, obesity, or use of assisted reproductive technology. There was an interaction between assisted reproductive technology and polycystic ovary syndrome for preterm birth. Since women with polycystic ovary syndrome often need assisted reproductive technology or ovulation induction to become pregnant, the risk of multiple births increases, which is associated with preterm birth. In previous reports the strongest predictor for preterm birth in women with polycystic ovary syndrome was multiple birth.14 A meta-analysis8 found a 75% increased risk of preterm birth in women with polycystic ovary syndrome, but when mean length of gestation was analysed women with polycystic ovary syndrome and controls did not differ. We found a higher proportion of macrosomia and being large for gestational age among infants of mothers with polycystic ovary syndrome. This finding is controversial since the available studies have not established this association.14 15 16 It is well founded that maternal obesity is associated with increased birth weight in offspring17 18 as well as glucose intolerance and gestational diabetes.19 Women with polycystic ovary syndrome are in general more overweight than women without the condition. The estimates in the present study were, however, adjusted for body mass index, suggesting that polycystic ovary syndrome may increase the rate of fetal growth independently. Women with polycystic ovary syndrome are, regardless of body mass index, at increased risk of developing gestational diabetes,8 20 supported by our finding. Infants born to mothers with polycystic ovary syndrome were more likely to have low Apgar scores at five minutes and to experience meconium aspiration. These infants may be more susceptible to fetal distress during labour. However, there was no association with stillbirth, and the increased risk for neonatal death was not statistically significant. These findings need to be confirmed in future studies. We observed a strong association between polycystic ovary syndrome and pre-eclampsia. Some studies have supported this finding,8 21 and others not.14 It is well stated that women undergoing assisted reproductive technology are at increased risk of hypertensive disease during pregnancy,22 23 which has been attributed to the underlying cause of infertility. In one study24 the risk of being born small for gestational age in the offspring of women with polycystic ovary syndrome was increased, whereas this could not be confirmed in other studies.14 15 16 We could not find any such correlation, suggesting that maternal polycystic ovary syndrome is not associated with growth restriction. The increased risk of caesarean section among women with polycystic ovary syndrome we found does not correspond with the findings of other studies. In a meta-analysis,8 women with polycystic ovary syndrome showed a significantly higher rate of caesarean section (odds ratio 1.56, 95% confidence interval 1.20 to 2.02), but in a subgroup analysis restricted to studies of higher validity no significant risk was observed (0.92, 0.54 to 1.58). Obesity has been shown to be an independent risk factor for caesarean delivery.25 In the present study, however, obesity was accounted for in the adjusted analysis. Women with polycystic ovary syndrome can conceive spontaneously but with a delayed fertile window since there is a tendency of regular menstrual cycles with advancing age.26 In the present study we found that women with polycystic ovary syndrome were slightly older than women without polycystic ovary syndrome. Advanced maternal age is strongly correlated with many of the adverse pregnancy outcomes in this study27; however, although we adjusted for maternal age in the multivariate analysis, a residual effect could still be possible.

Strengths and limitations of the study

A major strength of this study was the large sample size, making it possible to study rare pregnancy outcomes such as stillbirth, meconium aspiration, low Apgar scores at five minutes, and neonatal death. In this population based study we included women with pregnancies that were spontaneously conceived as well as conceived by assisted reproductive technology. Women with polycystic ovary syndrome according to the Rotterdam criteria,4 and not seeking medical assistance for irregular menstrual periods or infertility problems, might have been incorrectly classified as not having the disease. Such misclassification would lead to an underestimation of the association between polycystic ovary syndrome and adverse pregnancy outcomes. When the National Institutes of Health and Rotterdam criteria for polycystic ovary syndrome were compared, the prevalence was doubled.28 29 This may imply an underestimation of women with polycystic ovary syndrome at the start of the study period, when the National Institutes of Health criteria was used. However, we adjusted for calendar period in the multivariate analyses. Furthermore, it is likely that we included women with more severe disease as exposed, and the findings may consequently not be generalisable to all women with polycystic ovary syndrome.

Possible pathophysiological mechanisms

The pathophysiological mechanisms behind the increased risk of adverse pregnancy outcomes among women with polycystic ovary syndrome are not fully known. In this study, polycystic ovary syndrome was associated with being overweight and obese, with an increased risk of macrosomia and large for gestational age infants, even after adjustments for body mass index. A higher prevalence of pre-eclampsia and gestational diabetes may account for increased fetal stress leading to preterm birth, low Apgar scores at five minutes, and meconium aspiration. Women with polycystic ovary syndrome have increased levels of androgens, which have been associated with the development of pre-eclampsia.30 Metformin treatment during pregnancy does not seem to lower maternal androgen levels but has been shown to decrease severe pregnancy and post-partum complications, which may be mediated by reduced uterine artery impedance.31 32 Our results do not support the notion that assisted reproductive technology mediates adverse pregnancy outcomes among women with polycystic ovary syndrome. This finding is supported by a Norwegian study, which reported that adverse outcomes are attributable to the factors leading to infertility rather than to factors related to reproductive technology.33

Conclusions

In conclusion, women with polycystic ovary syndrome are at increased risk of adverse pregnancy and perinatal outcomes, which could not be explained by assisted reproductive technology. These women may need increased surveillance during pregnancy and parturition. Future research would benefit from focusing on glucose control, medical treatment, and hormonal status among women with polycystic ovary syndrome during pregnancy. Women with polycystic ovary syndrome undergoing assisted reproductive technology have increased risks of gestational diabetes, pre-eclampsia, and preterm birth Irrespective of the use of assisted reproduction, polycystic ovary syndrome is associated with preterm birth, gestational diabetes, and pre-eclampsia Infants born to mothers with polycystic ovary syndrome are more likely to have a low Apgar score at five minutes, have meconium aspiration, and be large for gestational age
  33 in total

1.  Estrogen and androgen concentrations are not lower in the umbilical cord serum of pre-eclamptic pregnancies.

Authors:  Rebecca Troisi; Nancy Potischman; Christine Neuser Johnson; James M Roberts; David Lykins; Gail Harger; Nina Markovic; Pentti Siiteri; Robert N Hoover
Journal:  Cancer Epidemiol Biomarkers Prev       Date:  2003-11       Impact factor: 4.254

2.  Obstetric outcome in women with polycystic ovarian syndrome.

Authors:  M Mikola; V Hiilesmaa; M Halttunen; L Suhonen; A Tiitinen
Journal:  Hum Reprod       Date:  2001-02       Impact factor: 6.918

3.  A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome.

Authors:  E M E W Heijnen; M J C Eijkemans; E G Hughes; J S E Laven; N S Macklon; B C J M Fauser
Journal:  Hum Reprod Update       Date:  2005-08-25       Impact factor: 15.610

4.  Are women with polycystic ovary syndrome at an increased risk of pregnancy-induced hypertension and/or preeclampsia?

Authors:  M Fridström; H Nisell; P Sjöblom; T Hillensjö
Journal:  Hypertens Pregnancy       Date:  1999       Impact factor: 2.108

5.  Pregnancy outcome in women with PCOS and in controls matched by age and weight.

Authors:  L Haakova; D Cibula; K Rezabek; M Hill; M Fanta; J Zivny
Journal:  Hum Reprod       Date:  2003-07       Impact factor: 6.918

6.  Polycystic ovaries and infertility: Our experience.

Authors:  Lavanya Rajashekar; Deepika Krishna; Madhuri Patil
Journal:  J Hum Reprod Sci       Date:  2008-07

7.  Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome.

Authors:  R S Legro; D Driscoll; J F Strauss; J Fox; A Dunaif
Journal:  Proc Natl Acad Sci U S A       Date:  1998-12-08       Impact factor: 11.205

8.  Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study.

Authors:  E Vanky; K A Salvesen; R Heimstad; K J Fougner; P Romundstad; S M Carlsen
Journal:  Hum Reprod       Date:  2004-06-03       Impact factor: 6.918

9.  Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study.

Authors:  E S Knochenhauer; T J Key; M Kahsar-Miller; W Waggoner; L R Boots; R Azziz
Journal:  J Clin Endocrinol Metab       Date:  1998-09       Impact factor: 5.958

10.  The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria.

Authors:  Wendy A March; Vivienne M Moore; Kristyn J Willson; David I W Phillips; Robert J Norman; Michael J Davies
Journal:  Hum Reprod       Date:  2009-11-12       Impact factor: 6.918

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Review 4.  PPAR-γ -- a possible drug target for complicated pregnancies.

Authors:  Fergus P McCarthy; Aoife C Delany; Louise C Kenny; Sarah K Walsh
Journal:  Br J Pharmacol       Date:  2013-03       Impact factor: 8.739

Review 5.  Psychiatric disorders in women with polycystic ovary syndrome: a systematic review and meta-analysis.

Authors:  Claire Brutocao; Feras Zaiem; Mouaz Alsawas; Allison S Morrow; M Hassan Murad; Asma Javed
Journal:  Endocrine       Date:  2018-07-31       Impact factor: 3.633

6.  Maternal High-Fat Diet Consumption and Chronic Hyperandrogenemia Are Associated With Placental Dysfunction in Female Rhesus Macaques.

Authors:  Kelly Kuo; Victoria H J Roberts; Jessica Gaffney; Diana L Takahashi; Terry Morgan; Jamie O Lo; Richard L Stouffer; Antonio E Frias
Journal:  Endocrinology       Date:  2019-08-01       Impact factor: 4.736

7.  Unaltered timing of embryo development in women with polycystic ovarian syndrome (PCOS): a time-lapse study.

Authors:  Linda Sundvall; Kirstine Kirkegaard; Hans Jakob Ingerslev; Ulla Breth Knudsen
Journal:  J Assist Reprod Genet       Date:  2015-05-01       Impact factor: 3.412

8.  Increased incidence of post-term delivery and Cesarean section after frozen-thawed embryo transfer during a hormone replacement cycle.

Authors:  Kazuki Saito; Kenji Miyado; Kenji Yamatoya; Akira Kuwahara; Eisuke Inoue; Mami Miyado; Maki Fukami; Tomonori Ishikawa; Takakazu Saito; Toshiro Kubota; Hidekazu Saito
Journal:  J Assist Reprod Genet       Date:  2017-01-20       Impact factor: 3.412

9.  Pregnancy Protects Hyperandrogenemic Female Rats From Postmenopausal Hypertension.

Authors:  Noha M Shawky; Chetan N Patil; Carolina Dalmasso; Rodrigo O Maranon; Damian G Romero; Heather Drummond; Jane F Reckelhoff
Journal:  Hypertension       Date:  2020-08-03       Impact factor: 10.190

10.  Irregular menstruation and hyperandrogenaemia in adolescence are associated with polycystic ovary syndrome and infertility in later life: Northern Finland Birth Cohort 1986 study.

Authors:  S West; H Lashen; A Bloigu; S Franks; K Puukka; A Ruokonen; M-R Järvelin; J S Tapanainen; L Morin-Papunen
Journal:  Hum Reprod       Date:  2014-08-01       Impact factor: 6.918

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