Objective
The purpose of this study was to examine which maternal and neonatal complications are associated with polycystic ovary syndrome (PCOS) in pregnant women.
Study Design
The studies that were included compared pregnancy outcomes between women with PCOS and those without diagnosed PCOS. Our primary outcomes included gestational diabetes mellitus, pregnancy-induced hypertension, and preeclampsia. Secondary outcomes included cesarean delivery rates, operative vaginal delivery rates, preterm delivery, small-for-gestational-age (SGA) infants and large-for-gestational-age infants.
Results
We found that PCOS in pregnancy was associated with higher rates of gestational diabetes mellitus, pregnancy-induced hypertension, preeclampsia, preterm delivery, cesarean delivery, operative vaginal delivery, SGA, and large-for-gestational age. Only gestational diabetes mellitus, pregnancy-induced hypertension, preeclampsia, preterm delivery, and SGA infants were found to be statistically significant.
Conclusion
This metaanalysis confirms the higher association of pregnancy complications and PCOS compared with patients who do not have PCOS. Additionally, there may be a stronger association between PCOS and hypertensive disorders than has been shown previously.
Polycystic ovary syndrome (PCOS) is estimated to affect at least 5–15% of reproductive-aged women and is therefore one of the most common endocrine abnormalities worldwide. Despite its prevalence, PCOS is a disease with an unclear cause, varying diagnostic criteria, expansive clinical effects, and debatable management. In nonpregnant women, PCOS is known to be associated with menstrual irregularities, decreased fertility, insulin resistance, diabetes mellitus, and hyperandrogenism. For this population to become pregnant, many women require assisted reproductive techniques in addition to the medical treatment of insulin insensitivity. Once this previously subfertile population becomes pregnant, the effect of maternal insulin insensitivity and hyperandrogenism on the fetus must be considered.
Pregnant women without PCOS have a natural state of insulin resistance. With the additive effect of PCOS, this baseline insulin resistance may worsen and lead to gestational diabetes mellitus and its consequences. Additionally, women with PCOS have been shown to have a low amount of insulin-like growth factor binding globulin-1 that may contribute to preeclampsia and growth abnormalities. An earlier metaanalysis in 2006 found that women with PCOS had a significantly higher risk of experiencing gestational diabetes mellitus, pregnancy-induced hypertension, preeclampsia, and preterm birth. Additionally, infants of women with PCOS also had a significantly higher risk of admission to a neonatal intensive care unit and a higher perinatal mortality rate that was unrelated to multiple births. Since that report, 8 relevant studies have been published, which includes one that has disputed the increased risk of preeclampsia, preterm delivery, polyhydramnios, oligohydramnios, macrosomia, and adverse infant outcomes. In view of these new reports, we conducted an updated metaanalysis to reevaluate the risks of gestational diabetes mellitus, pregnancy-induced hypertension, preeclampsia, cesarean delivery, preterm delivery, and operative vaginal delivery.
Materials and Methods
We reviewed computerized databases, references of published articles, and textbook chapters to find articles that would meet the inclusion criteria. Computerized databases included MEDLINE (Pubmed, NLM Gateway) and Cochrane Library.
Study selection
To examine the association between PCOS and pregnancy complications, we searched for studies from 1966 to April 2010 in which outcomes were compared between women with PCOS and women without diagnosed PCOS. Because most of the studies were performed before the revised 2006 Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society criteria, the 2003 Rotterdam criteria were used to establish the diagnosis of PCOS. Specifically, the Rotterdam criteria require at least 2 of 3 features of PCOS: (1) oligomenorrhea and/or anovulation, (2) clinical and/or biochemical signs of hyperandrogenism, (3) polycystic ovaries on ultrasound scanning. The revised 2006 AE-PCOS criteria excluded patients who were not hyperandrogenic with only oligo/anovulation and polycystic ovaries on ultrasound scanning from the diagnosis of PCOS but included the other phenotypes of PCOS that had been determined by the Rotterdam consensus. Because the 2006 AE-PCOS criteria are inherently within the definition of the Rotterdam criteria, these updated criteria were used as an acceptable alternative to use to diagnose PCOS in the more current articles. Our primary outcomes included gestational diabetes mellitus, pregnancy-induced hypertension, and preeclampsia. Secondary outcomes included cesarean delivery rates, operative vaginal delivery rates, preterm delivery, small-for-gestational age infants, and large-for-gestational age infants.
Tabulation and integration
This systematic review was preceded by a detailed study protocol that stated the question to be addressed, the subgroups of interest, and the methods and criteria to be used for the identification and selection of relevant studies and extraction and analysis of information. Approval from the institutional review board was not required to perform this metaanalysis. With the use of computerized databases, references of published systematic reviews, and textbook chapters, potential articles were found and reviewed. Search terms included PCOS and pregnancy complications, PCOS and pregnancy outcomes, PCOS and neonatal outcomes, PCOS and gestational diabetes mellitus, PCOS and pregnancy and hypertension, PCOS and preeclampsia, PCOS and preterm labor, PCOS and cesarean section delivery, PCOS and operative vaginal delivery, PCOS and forceps, and PCOS and vacuum delivery.
Articles that were included for full review required the following information: (1) assessment of obstetric outcomes in women with PCOS that had been diagnosed by the Rotterdam criteria or the updated 2006 AE-PCOS criteria, (2) assessment of obstetric outcomes in women without PCOS, and (3) metformin could not have been used by the PCOS group after conception. We followed the Meta-analysis of Observational Studies in Epidemiology group guidelines for analyzing observational studies in a metaanalysis. Two contributors independently assessed each article, and any discrepancies were discussed with 1 of 2 other contributors.
Results
Initial broad search results yielded 946 possible articles ( Figure ). Later, 897 articles were excluded because of duplication or irrelevance by title; then 12 articles were excluded on the basis of the abstract. Of the remaining, 37 articles, 14 articles were excluded because 4 lacked a comparison group, 2 did not evaluate the included outcomes, and 8 involved the use of metformin after diagnosis of pregnancy. The final 23 articles that fully met inclusion criteria were then reviewed, and data tables were constructed. A total of 92,392 patients were included in the metaanalysis (2544 patients with PCOS compared with 89,848 patients without PCOS). Table 1 shows the characteristics of each study. Women with PCOS were noted to have higher rates of gestational diabetes mellitus (odds ratio [OR], 2.82; 95% confidence interval [CI], 1.93–4.10), pregnancy-induced hypertension (OR, 4.07; 95% CI, 2.75–6.02), preeclampsia (OR, 4.23; 95% CI, 2.77–6.46), preterm delivery (OR, 2.20; 95% CI, 1.59–3.04), cesarean delivery (OR, 1.41; 95% CI, 0.96–2.07), operative vaginal delivery (OR, 1.56; 95% CI, 0.93–2.63), small-for-gestational-age infants (OR, 2.62; 95% CI, 1.35–5.10), and large-for-gestational-age infants (OR, 1.56; 95% CI, 0.92–2.64). Table 2 summarizes these results. Tables 3-5 specifically outline the odds ratio for the primary outcomes. All pregnancy outcomes, except for gestational diabetes mellitus, were evaluated with the use of a fixed-effects model in which the random-effects model was used. We used Stata software (version11.0; StataCorp, College Station, TX) to perform the metaanalysis.
| Group, n | |||||
|---|---|---|---|---|---|
| Study | Outcomes included | Women with polycystic ovary syndrome | Control patients | Conception method | Study type |
| Altieri et al | GDM, PIH, preeclampsia, cesarean delivery, OVD, PTD, neonatal malformation | 15 | 159 | Spontaneous, ovulation induction, ART | Retrospective |
| Hu et al | PIH, preeclampsia | 22 | 22 | Spontaneous | Prospective |
| Li et al | Preeclampsia, PTD, macrosomia, LGA, SGA | 34 | 70 | Spontaneous and ART | Prospective |
| Maliqueo et al | LGA, SGA | 30 | 34 | Spontaneous | Prospective |
| Palomba et al | GDM, PIH, preeclampsia, cesarean delivery, OVD, PTD, LGA, SGA, placental abruption | 93 | 69 | Spontaneous | Prospective |
| Diamant et al | Preeclampsia | 70 | 71 | Ovulation induction | Retrospective |
| Levran et al | GDM | 76 | 95 | Spontaneous, ovulation induction | Retrospective |
| Wortsman et al | GDM | 53 | 2306 | Spontaneous, ovulation induction | Retrospective |
| Cardenas et al | GDM | 31 | 78 | Ovulation induction | Retrospective |
| Urman et al | GDM, PIH, preeclampsia, PTD, NICU admission | 47 | 100 | Spontaneous, ovulation induction, ART | Retrospective |
| Fridstrom et al | GDM, PIH, preeclampsia | 33 | 66 | Spontaneous, ovulation induction, ART | Retrospective |
| Radon et al | GDM, preeclampsia | 22 | 66 | Spontaneous, ovulation induction, ART | Retrospective |
| Kashyap and Claman | PIH | 22 | 27 | Spontaneous, ovulation induction, ART | Retrospective |
| Vollenhoven et al | GDM, PIH, PTD | 60 | 60 | Spontaneous, ovulation induction | Retrospective |
| Mikola et al | GDM, PIH, PTD | 80 | 712 | Ovulation induction | Retrospective |
| Bjercke et al | GDM, PIH, preeclampsia, cesarean delivery, OVD, PTD, NICU admission | 52 | 335 | Ovulation induction, ART | Prospective |
| Haakova et al | GDM, PIH, cesarean delivery, PTD | 66 | 66 | Spontaneous, unspecified ART | Retrospective |
| Turhan et al | GDM, PIH, preeclampsia, cesarean delivery, PTD, macrosomia, neonatal malformation, abruption | 38 | 136 | Not stated | Retrospective |
| Weerakiet et al | GDM, PIH, preeclampsia, PTD | 39 | 219 | Spontaneous, ovulation induction, ART | Prospective |
| Sir-Peterman et al | GDM, preeclampsia, PTD, LGA, SGA | 47 | 180 | Spontaneous, unspecified ART | Prospective |
| Lesser and Garcia | GDM | 24 | 44 | Unspecified ART | Retrospective |
| Lo et al | GDM | 1542 | 84882 | Not stated | Retrospective |
| Sir-Peterman et al | GDM, PIH | 48 | 51 | Not stated | Prospective |
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