Pregnancy outcomes in women with polycystic ovary syndrome: a metaanalysis




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.




FIGURE


Flowchart of study selection

Kjerulff. Pregnancy outcomes and polycystic ovary syndrome. Am J Obstet Gynecol 2011.


TABLE 1

Characteristics of included studies


















































































































































































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

ART , assisted reproductive technique; GDM , gestational diabetes mellitus; LGA , large-for-gestational age; NICU , neonatal intensive care unit; OVD , operative vaginal delivery; PIH , pregnancy-induced hypertension; PTD , preterm delivery; SGA , small-for-gestational age.

Kjerulff. Pregnancy outcomes and polycystic ovary syndrome. Am J Obstet Gynecol 2011.

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May 28, 2017 | Posted by in GYNECOLOGY | Comments Off on Pregnancy outcomes in women with polycystic ovary syndrome: a metaanalysis

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