http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2015; 28(4): 475–478 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.921673
ORIGINAL ARTICLE
Obstetric outcomes in women with polycystic ovary syndrome and isolated polycystic ovaries undergoing in vitro fertilization: a retrospective cohort analysis J Matern Fetal Neonatal Med 2015.28:475-478. Downloaded from informahealthcare.com by Kainan University on 04/18/15. For personal use only.
Hei Lok Tiffany Wan, Pui Wah Hui, Hang Wun Raymond Li, and Ernest Hung Yu Ng Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong
Abstract
Keywords
Objective: This retrospective cohort study evaluated the obstetric outcomes in women with polycystic ovary syndrome (PCOS) and isolated polycystic ovaries (PCO) undergoing in vitro fertilization (IVF) treatment. Methods: We studied 104 women with PCOS, 184 with PCO and 576 age-matched controls undergoing the first IVF treatment cycle between 2002 and 2009. Obstetric outcomes and complications including gestational diabetes (GDM), gestational hypertension (GHT), gestational proteinuric hypertension (PET), intrauterine growth restriction (IUGR), gestation at delivery, baby’s Apgar scores and admission to the neonatal intensive care unit (NICU) were reviewed. Results: Among the 864 patients undergoing IVF treatment, there were 253 live births in total (25 live births in the PCOS group, 54 in the PCO group and 174 in the control group). The prevalence of obstetric complications (GDM, GHT, PET and IUGR) and the obstetric outcomes (gestation at delivery, birth weight, Apgar scores and NICU admissions) were comparable among the three groups. Adjustments for age and multiple pregnancies were made using multiple logistic regression and we found no statistically significant difference among the three groups. Conclusion: Patients with PCO ± PCOS do not have more adverse obstetric outcomes when compared with non-PCO patients undergoing IVF treatment.
Isolated polycystic ovaries, IVF, obstetric outcomes, PCOS
Introduction Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women of reproductive age, affecting between 10% and 15% of women overall [1,2]. The syndrome is characterized clinically by oligomenorrhoea, hyperandrogenism, and the typical ultrasonographic appearance of polycystic ovaries (PCO). Women with two out of the three described features are diagnosed to have PCOS according to the Rotterdam criteria [3]. Other manifestations of PCOS include hyperinsulinaemia [1], glucose intolerance [4], obesity [5] and hyperlipidaemia [6]. Ovulation induction (OI) treatment is generally offered to women with PCOS associated with anovulatory subfertility [7]. However, assisted reproductive technologies (ART) may be required in case of failure of OI treatment [4] or when there is co-existing tubal or male factor. A meta-analysis showed that PCOS pregnancies were associated with more adverse Address for correspondence: Dr. Hei Lok Tiffany Wan, Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong. Tel: +852 22553111. Fax: +852 28550947. E-mail: [email protected]
History Received 3 January 2014 Revised 14 April 2014 Accepted 2 May 2014 Published online 29 May 2014
obstetrics and neonatal outcomes including gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), pre-eclampsia, preterm delivery and higher perinatal mortality [8]; however, other groups suggested the risks varied widely according to the different phenotypes and features of PCOS [9,10]. Polycystic ovaries on ultrasound scan are one of the key features of PCOS, but this finding can be non-specific as it may also be seen in ovulatory women [11]. The significance of isolated PCO morphology in women’s reproductive and metabolic outcome has been controversial [11,12], and there is a paucity of data in the literature evaluating the obstetric and neonatal outcomes in women with isolated PCO undergoing ART. The aim of this study was to compare the obstetric and neonatal outcomes in women with PCOS and isolated PCO undergoing in vitro fertilization (IVF) treatment with age-matched controls.
Methods This was a retrospective study carried out at the Centre of Assisted Reproduction and Embryology, The University of
476
H. L. T. Wan et al.
Hong Kong – Queen Mary Hospital, Hong Kong. Clinical details of all treatment cycles were prospectively entered into a computerized database, which were checked for accuracy and completeness on a regular basis and were retrieved for analysis. Ethical approval was obtained from the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster for this retrospective study.
J Matern Fetal Neonatal Med 2015.28:475-478. Downloaded from informahealthcare.com by Kainan University on 04/18/15. For personal use only.
Selection of patients We reviewed the data of infertile women who underwent their first IVF cycle using long GnRH agonist protocol between January 2002 and December 2009. Among this cohort, we identified 104 women with PCOS and 184 women with isolated PCO and documented regular ovulation with no evidence of hyperandrogenism. The diagnosis of PCOS was made according to the Rotterdam criteria [3]. Androgen profile, insulin resistance and oral glucose tolerance test were not routinely checked in our cohort of women, and the diagnosis of PCOS was mostly based on the presence of oligomenorrhoea and PCO on ultrasound. All women in our study did not have clinical signs of hyperandrogenism. PCO was defined by the presence of 12 or more antral follicles of 2–9 mm on transvaginal ultrasonography [13]. Another 576 age-matched ovulatory non-PCO women were selected as the control group. Stimulation protocols and embryo transfer The details of the long GnRH protocol of ovarian stimulation regimen, gamete handling, standard insemination and intracytoplasmic sperm injection (ICSI) were as previously described [14]. In short, women received buserulin (SuprecurÕ ; Hoechst, Frankfurt, Germany) nasal spray 150 mg four times a day starting from the mid-luteal phase of the cycle preceding the treatment cycle, and received human menopausal gonadotrophin (hMG) or recombinant follicular stimulating hormone (FSH) for ovarian stimulation following the menstrual period. The doses used for stimulation were adjusted according to the baseline antral follicle count. Transvaginal ultrasonography and measurement of blood estradiol levels were used to assess ovarian response. When the mean diameter of the leading follicle reached 18 mm and there are at least three follicles reaching a mean diameter of 16 mm or more, HCG [PregnylÕ (Organon, Oss, Holland)] 5000 or 10 000 units or Ovidrel [(Merck Serono S.p.A., Modugno, Italy) 250 mg] was injected on the same day and oocytes were collected 36 h later. Fertilization was carried out in vitro either by conventional insemination or by ICSI depending on semen parameters. Women were allowed to have replacement of at most three embryos before 2006 and up to two embryos in 2006 onwards 2 days after oocytes retrieval. Progesterone pessaries of Cyclogest [(400 mg twice daily), Cox Pharmaceuticals, Barnstaple, UK] or Endometrin [(100 mg twice daily), Ferring Pharmaceuticals, Parsippany, NJ] were administered from the day of embryo transfer for 2 weeks for luteal support. Pregnancies were confirmed by positive urine HCG tests and transvaginal ultrasonographic evidence of positive fetal heart pulsation subsequently.
J Matern Fetal Neonatal Med, 2015; 28(4): 475–478
Collection of clinical information Clinical information including age and body mass index were collected. Only pregnant women with an ongoing pregnancy at 12-week gestation were included for analysis. Live birth was defined as the delivery of a fetus with signs of life after 24 completed weeks of gestational age. Pregnancy and neonatal outcomes were collected from medical records, postal questionnaire or by phone. The diagnosis of gestational diabetes mellitus was made with the 2-h 75 g oral glucose tolerance test (OGTT) using the criteria defined by the World Health Organization [15]. The definitions of pregnancy-induced hypertension (blood pressure 140/90 mmHg without proteinuria at a gestational age 420 weeks on two or more occasions at least 4 h apart), preeclampsia (blood pressure 140/90 mmHg in combination with proteinuria 40.3 g/24 h after 20 weeks gestation), and small-for-gestational age (birth weight less than the 10th centile) were the same as those used by the Royal College of Obstetricians and Gynaecologists [16,17]. Preterm birth referred to a birth occurring before 37 weeks of gestation. Congenital abnormalities included all structural anomalies. Statistical analysis Statistical analysis for the comparisons of mean values was performed using Mann–Whitney test or Student’s t-test as appropriate. The chi-squared test or Fisher’s exact test were used for the comparisons of categorical variables. Logistic regression analysis was used to adjust for age and multiple pregnancies. All analyses were carried out using the Statistical Program for Social Sciences (Version 20.0; SPSS Inc., Chicago, IL) and MedCalc (Version 12, Belgium). The two-tailed value of p50.05 was considered statistically significant.
Results Among the 864 women included in this study, 253 of them achieved a live birth with an overall live birth rate of 29.3% (25 in the PCOS group, 54 in the PCO group and 174 in control group). Women with PCOS were the youngest among the three groups (p50.05) but other characteristics were comparable (Table 1). The characteristics of IVF cycle and IVF outcomes including pregnancy rates, miscarriage rates and live birth rates were not examined and reported in this report. A comparison among the three groups did not reveal a significant difference in the prevalence of maternal obstetrics complications including GDM, PIH, preeclampsia and preterm delivery, even after adjustment for age and multiple pregnancies (Table 2). As for the neonatal complications, the birth weight, Apgar score at 1 and 5 min, admission to special baby care unit (SBCU) and admission to neonatal intensive care unit (NICU) were similar among the three groups (Table 3).
Discussion Many studies have reported on the obstetric and neonatal complications in women with PCOS, but there was paucity of data in the literature regarding the obstetric and neonatal
Women with PCOS and isolated polycystic ovaries
DOI: 10.3109/14767058.2014.921673
477
Table 1. Baseline characteristics. p value Control (n ¼ 174) PCOS (n ¼ 25) PCO (n ¼ 54) Overall PCOS versus control PCO versus control PCOS versus PCO
Group Age (years) BMI (kg/m2) Duration of infertility Primary subfertility
32.7 ± 3.1 21.5 ± 2.6 4.6 ± 2.7 115 (66.1)
31.4 ± 2 22.8 ± 3.6 3.9 ± 1.7 17 (68.0)
34.2 ± 2.8 21.2 ± 2.0 4.7 ± 2.8 39 (72.2)
50.001 NS NS NS
40.002
0.043
50.001
Data expressed as mean ± SD or n (%).
Table 2. Obstetrics complications.
J Matern Fetal Neonatal Med 2015.28:475-478. Downloaded from informahealthcare.com by Kainan University on 04/18/15. For personal use only.
Control (n ¼ 171) GDM (%) GHT (%) PET (%) IUGR (%) Preterm (%) Congenital abnormality (%)
52 6 7 11 42 12
(30.4) (3.5) (4.1) (6.5) (24.6) (7.5)
PCOS (n ¼ 24) 7 2 2 3 6 3
(29.2) (8.3) (8.3) (12.5) (25.0) (12.5)
PCO (n ¼ 53)
p value
16 (30.2) 0 1 (1.9) 6 (11.3) 8 (15.1) 0
NS NS (0.15) NS (0.41) NS (0.37) NS (0.34) NS (0.064)
Adjusted p value* NS NS NS NS NS NS
(0.99) (0.53) (0.38) (0.40) (0.24) (0.66)
*Adjusted for age and multiple pregnancy.
Table 3. Obstetrics outcomes.
Gestation at delivery (weeks) Birth weight (g) Apgar score at 1 min 55 (%) Apgar score at 5 min 57 (%) SCBU admission (%) NICU admission (%)
Control (n ¼ 171)
PCOS (n ¼ 24)
PCO (n ¼ 53)
37.2 ± 3.0 2701 ± 671 4 (3.1) 1 (0.8) 44 (32.1) 23 (16.8)
37.7 ± 2.4 2722 ± 628 0 0 6 (31.6) 2 (10.5)
37.6 ± 2.7 2737 ± 668 1 (2.8) 1 (2.9) 9 (25.7) 5 (14.3)
p value NS NS NS NS NS NS
(0.51) (0.98) (0.72) (0.51) (0.76) (0.76)
Adjusted p value* NS NS NS NS NS NS
(0.77) (0.64) (0.33) (0.20) (0.35) (0.26)
*Adjusted for age and multiple pregnancy.
outcomes of women with isolated PCO morphology. To our best knowledge, this was the first study to look at the perinatal outcome in women with isolated PCO, and to compare them with PCOS women and women with normal ovaries. In our study, we did not find a significant difference in the pregnancy and neonatal outcomes among women with PCOS, isolated PCO and the non-PCO controls after adjusting for age and multiple pregnancies. PCOS has been associated with negative pregnancy outcome but interpretation of previous studies has been limited by different study designs, inconsistent diagnostic criteria for PCOS and selection of the control group [8]. The negative impact was thought to be related to the metabolic abnormalities such as insulin resistance and hyperandrogenism in PCOS women, and therefore they had a tendency to develop GDM, PIH and preeclampsia. Sayin et al. [12] showed that some women with PCO shared some endocrine abnormalities with those with PCOS, but others have shown that ovulatory PCO women did not express similar abnormalities as PCOS women and that PCO might only represent some normal variation in the ovarian morphology [18]. Our study showed that both the PCOS and isolated PCO groups did not have adverse pregnancy and birth outcomes when compared with controls, and the results were consistent with studies focusing on PCOS women when age and weight were adjusted for [19]. Isolated PCO might be regarded as a normal variation of ovarian morphology, as suggested by a previous
study [18]. However, our study is limited by the fact that women with isolated PCO were not evaluated endocrinologically albeit having regular ovulatory cycle and no evidence of clinical hyperandrogenism. The inconsistence of our findings in PCOS group with those from previous meta-analyses may be explained by the fact that majority of our patients do not suffer from obesity and clinical hyperandrogenism, which were the two key features that were thought to be associated with adverse pregnancy outcomes. The mean BMI were 523 kg/m2 in each group and they were comparable among the three groups. This could possibly explain the similar prevalence of complications in the groups, as obesity is known to be a major risk factor associated with adverse pregnancy outcomes [20]. The world-wide prevalence of GDM ranges from 1% to 14% [21], depending on which population is being screened and which screening strategies and diagnostic criteria are used [22]. Our prevalence of 30% in all groups was relatively high compared to the world-wide figures, but comparable to our local data and consistent with other studies reporting higher prevalence in Asians [23,24]. Limitations of the study include the small sample size, the retrospective study design and the timing of selection of the age-matched controls. A better design would be using ageand weight-matched controls selected from women who had undergone their first prenatal ultrasound examination after successful IVF treatment rather than before IVF stimulation.
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J Matern Fetal Neonatal Med 2015.28:475-478. Downloaded from informahealthcare.com by Kainan University on 04/18/15. For personal use only.
Recent studies have looked at obstetric and neonatal outcomes in PCOS women with different phenotypes. These studies showed that increased risk for adverse obstetric and neonatal outcomes in patients with PCOS varies widely according to the different phenotypes and features of PCOS, with a higher incidence in hyperandrogenic PCOS women [9,25]. Our study is concordant with their findings that there was no significant effect on obstetric and neonatal outcomes for nonhyperandrogenic PCOS women (RR 0.54, 95% CI 0.09–1.63). In conclusion, our current study confirms that women with isolated PCO do not have an increased risk for adverse obstetric or neonatal outcomes, and it may be a normal variation of ovary morphology. Further studies with a larger sample size analyzing PCOS women according to different phenotypes would give us a better understanding on its significance.
Declaration of interest The authors report no declarations of interest.
References 1. Archer JS, Chang RJ. Hirsutism and acne in polycystic ovary syndrome. Best Pract Res Clin Obstet Gynecol 2004;18:737–54. 2. Azziz R, Woods KS, Reyna R, et al. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004;89:2745–9. 3. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41–7. 4. Ehrmann DA, Barnes RB, Rosenfield RL, et al. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 1999;22:141–6. 5. Norman RJ, Noakes M, Wu R, et al. Improving reproductive performance in overweight/obese women with effect weight management. Hum Reprod Update 2004;10:267–80. 6. Wild RA, Painter PC, Coulson PB, et al. Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1985;61:946–51. 7. Shulman A, Dor J. In vitro fertilization treatment in patients with polycystic ovaries. J Assist Reprod Genet 1997;14:7–10. 8. Boomsma CM, Eijkemans MJC, Hughes EG, et al. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod Update 2006;12:673–83. 9. Palomba S, Falbo A, Russo T, et al. Pregnancy in women with polycystic ovary syndrome: the effect of different phenotypes and features on obstetric and neonatal outcomes. Fertil Steril 2010;94: 1805–11.
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10. Han AR, Kim HO, Cha SW, et al. Adverse pregnancy outcomes with assisted reproductive technology in non-obese women with polycystic ovary syndrome: a case-control study. Clin Exp Reprod Med 2011;38:103–8. 11. Jonestone EB, Rosen MP, Neril R, et al. The polycystic ovary postrotterdam: a common, age-dependent finding in ovulatory women without metabolic significance. J Clin Endocrinol Metab 2010;95: 4965–72. 12. Sayin NC, Cucer F, Balkanli-Kaplan P, et al. Insulin resistance and lipid profile in women with polycystic appearing ovaries: implications with regard to polycystic ovary syndrome. Gynecol Endocrinol 2003;17:387–96. 13. Balen AH, Laven JS, Tan SL, et al. Ultrasound assessment of the polycystic ovary: international consensus definitions. Hum Reprod Update 2003;9:505–14. 14. Li HW, Lee CY, Lau YL, et al. Cumulative live-birth rate in women with polycystic ovary syndrome or isolated polycystic ovaries undergoing in-vitro fertilization treatment. J Assist Reprod Genet 2014;31:205–11. 15. WHO Consultation: Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO consultation. Part I: diagnosis and classification of diabetes mellitus. Geneva: World Health Organization; 1999. 16. Royal College of Obstetricians and Gynecologists. The management of pre-eclampsia/eclampsia. Green-top Guideline No. 10A. London: RCOG; 2006. 17. Royal College of Obstetricians and Gynecologists. Smallfor-gestational-age fetus, investigation and management. Greentop Guideline No. 31. London: RCOG; 2013. 18. Zhong YP, Ying Y, Wu HT, et al. Comparison of endocrine profile and in vitro fertilization outcomes in patients with PCOS, ovulatory PCO, or normal ovaries. Int J Endocrinol 2012;2012:492803. 19. Haakova L, Cibula D, Rezabek K, et al. Pregnancy outcome in women with PCOS and in controls matched by age and weight. Hum Reprod 2003;18:1438–41. 20. Athukorala C, Rumbold AR, Willson KJ, Crowther CA. The risk of adverse pregnancy outcomes in women who are overweight or obese. BMC Pregnancy Childbirth 2010;10:56. 21. American Diabetes Association. Gestational diabetes mellitus. Diabetes Care 2004;27:S88–90. 22. Agarwal MM, Dhatt GS, Punnose J, Koster G. Gestational diabetes: dilemma caused by multiple international diagnostic criteria. Diabet Med 2005;22:1731–6. 23. Lao TT, Ho LF, Chan BCP, Leung WC. Maternal age and prevalence of gestational diabetes mellitus. Diabetes Care 2006;29: 948–9. 24. Makgoba M, Savvidou MD, Steer PJ. An analysis of the interrelationship between maternal age, body mass index and racial origin in the development of gestational diabetes mellitus. BJOG 2012;119: 276–82. 25. Altieri P, Gambineri A, Prontera O, et al. Maternal polycystic ovary syndrome may be associated with adverse pregnancy outcomes. Eur J Obstet Gynecol Reprod Biol 2010;149:31–6.
ORIGINAL ARTICLE
Obstetric outcomes in women with polycystic ovary syndrome and isolated polycystic ovaries undergoing in vitro fertilization: a retrospective cohort analysis J Matern Fetal Neonatal Med 2015.28:475-478. Downloaded from informahealthcare.com by Kainan University on 04/18/15. For personal use only.
Hei Lok Tiffany Wan, Pui Wah Hui, Hang Wun Raymond Li, and Ernest Hung Yu Ng Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong
Abstract
Keywords
Objective: This retrospective cohort study evaluated the obstetric outcomes in women with polycystic ovary syndrome (PCOS) and isolated polycystic ovaries (PCO) undergoing in vitro fertilization (IVF) treatment. Methods: We studied 104 women with PCOS, 184 with PCO and 576 age-matched controls undergoing the first IVF treatment cycle between 2002 and 2009. Obstetric outcomes and complications including gestational diabetes (GDM), gestational hypertension (GHT), gestational proteinuric hypertension (PET), intrauterine growth restriction (IUGR), gestation at delivery, baby’s Apgar scores and admission to the neonatal intensive care unit (NICU) were reviewed. Results: Among the 864 patients undergoing IVF treatment, there were 253 live births in total (25 live births in the PCOS group, 54 in the PCO group and 174 in the control group). The prevalence of obstetric complications (GDM, GHT, PET and IUGR) and the obstetric outcomes (gestation at delivery, birth weight, Apgar scores and NICU admissions) were comparable among the three groups. Adjustments for age and multiple pregnancies were made using multiple logistic regression and we found no statistically significant difference among the three groups. Conclusion: Patients with PCO ± PCOS do not have more adverse obstetric outcomes when compared with non-PCO patients undergoing IVF treatment.
Isolated polycystic ovaries, IVF, obstetric outcomes, PCOS
Introduction Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women of reproductive age, affecting between 10% and 15% of women overall [1,2]. The syndrome is characterized clinically by oligomenorrhoea, hyperandrogenism, and the typical ultrasonographic appearance of polycystic ovaries (PCO). Women with two out of the three described features are diagnosed to have PCOS according to the Rotterdam criteria [3]. Other manifestations of PCOS include hyperinsulinaemia [1], glucose intolerance [4], obesity [5] and hyperlipidaemia [6]. Ovulation induction (OI) treatment is generally offered to women with PCOS associated with anovulatory subfertility [7]. However, assisted reproductive technologies (ART) may be required in case of failure of OI treatment [4] or when there is co-existing tubal or male factor. A meta-analysis showed that PCOS pregnancies were associated with more adverse Address for correspondence: Dr. Hei Lok Tiffany Wan, Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong. Tel: +852 22553111. Fax: +852 28550947. E-mail: [email protected]
History Received 3 January 2014 Revised 14 April 2014 Accepted 2 May 2014 Published online 29 May 2014
obstetrics and neonatal outcomes including gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), pre-eclampsia, preterm delivery and higher perinatal mortality [8]; however, other groups suggested the risks varied widely according to the different phenotypes and features of PCOS [9,10]. Polycystic ovaries on ultrasound scan are one of the key features of PCOS, but this finding can be non-specific as it may also be seen in ovulatory women [11]. The significance of isolated PCO morphology in women’s reproductive and metabolic outcome has been controversial [11,12], and there is a paucity of data in the literature evaluating the obstetric and neonatal outcomes in women with isolated PCO undergoing ART. The aim of this study was to compare the obstetric and neonatal outcomes in women with PCOS and isolated PCO undergoing in vitro fertilization (IVF) treatment with age-matched controls.
Methods This was a retrospective study carried out at the Centre of Assisted Reproduction and Embryology, The University of
476
H. L. T. Wan et al.
Hong Kong – Queen Mary Hospital, Hong Kong. Clinical details of all treatment cycles were prospectively entered into a computerized database, which were checked for accuracy and completeness on a regular basis and were retrieved for analysis. Ethical approval was obtained from the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster for this retrospective study.
J Matern Fetal Neonatal Med 2015.28:475-478. Downloaded from informahealthcare.com by Kainan University on 04/18/15. For personal use only.
Selection of patients We reviewed the data of infertile women who underwent their first IVF cycle using long GnRH agonist protocol between January 2002 and December 2009. Among this cohort, we identified 104 women with PCOS and 184 women with isolated PCO and documented regular ovulation with no evidence of hyperandrogenism. The diagnosis of PCOS was made according to the Rotterdam criteria [3]. Androgen profile, insulin resistance and oral glucose tolerance test were not routinely checked in our cohort of women, and the diagnosis of PCOS was mostly based on the presence of oligomenorrhoea and PCO on ultrasound. All women in our study did not have clinical signs of hyperandrogenism. PCO was defined by the presence of 12 or more antral follicles of 2–9 mm on transvaginal ultrasonography [13]. Another 576 age-matched ovulatory non-PCO women were selected as the control group. Stimulation protocols and embryo transfer The details of the long GnRH protocol of ovarian stimulation regimen, gamete handling, standard insemination and intracytoplasmic sperm injection (ICSI) were as previously described [14]. In short, women received buserulin (SuprecurÕ ; Hoechst, Frankfurt, Germany) nasal spray 150 mg four times a day starting from the mid-luteal phase of the cycle preceding the treatment cycle, and received human menopausal gonadotrophin (hMG) or recombinant follicular stimulating hormone (FSH) for ovarian stimulation following the menstrual period. The doses used for stimulation were adjusted according to the baseline antral follicle count. Transvaginal ultrasonography and measurement of blood estradiol levels were used to assess ovarian response. When the mean diameter of the leading follicle reached 18 mm and there are at least three follicles reaching a mean diameter of 16 mm or more, HCG [PregnylÕ (Organon, Oss, Holland)] 5000 or 10 000 units or Ovidrel [(Merck Serono S.p.A., Modugno, Italy) 250 mg] was injected on the same day and oocytes were collected 36 h later. Fertilization was carried out in vitro either by conventional insemination or by ICSI depending on semen parameters. Women were allowed to have replacement of at most three embryos before 2006 and up to two embryos in 2006 onwards 2 days after oocytes retrieval. Progesterone pessaries of Cyclogest [(400 mg twice daily), Cox Pharmaceuticals, Barnstaple, UK] or Endometrin [(100 mg twice daily), Ferring Pharmaceuticals, Parsippany, NJ] were administered from the day of embryo transfer for 2 weeks for luteal support. Pregnancies were confirmed by positive urine HCG tests and transvaginal ultrasonographic evidence of positive fetal heart pulsation subsequently.
J Matern Fetal Neonatal Med, 2015; 28(4): 475–478
Collection of clinical information Clinical information including age and body mass index were collected. Only pregnant women with an ongoing pregnancy at 12-week gestation were included for analysis. Live birth was defined as the delivery of a fetus with signs of life after 24 completed weeks of gestational age. Pregnancy and neonatal outcomes were collected from medical records, postal questionnaire or by phone. The diagnosis of gestational diabetes mellitus was made with the 2-h 75 g oral glucose tolerance test (OGTT) using the criteria defined by the World Health Organization [15]. The definitions of pregnancy-induced hypertension (blood pressure 140/90 mmHg without proteinuria at a gestational age 420 weeks on two or more occasions at least 4 h apart), preeclampsia (blood pressure 140/90 mmHg in combination with proteinuria 40.3 g/24 h after 20 weeks gestation), and small-for-gestational age (birth weight less than the 10th centile) were the same as those used by the Royal College of Obstetricians and Gynaecologists [16,17]. Preterm birth referred to a birth occurring before 37 weeks of gestation. Congenital abnormalities included all structural anomalies. Statistical analysis Statistical analysis for the comparisons of mean values was performed using Mann–Whitney test or Student’s t-test as appropriate. The chi-squared test or Fisher’s exact test were used for the comparisons of categorical variables. Logistic regression analysis was used to adjust for age and multiple pregnancies. All analyses were carried out using the Statistical Program for Social Sciences (Version 20.0; SPSS Inc., Chicago, IL) and MedCalc (Version 12, Belgium). The two-tailed value of p50.05 was considered statistically significant.
Results Among the 864 women included in this study, 253 of them achieved a live birth with an overall live birth rate of 29.3% (25 in the PCOS group, 54 in the PCO group and 174 in control group). Women with PCOS were the youngest among the three groups (p50.05) but other characteristics were comparable (Table 1). The characteristics of IVF cycle and IVF outcomes including pregnancy rates, miscarriage rates and live birth rates were not examined and reported in this report. A comparison among the three groups did not reveal a significant difference in the prevalence of maternal obstetrics complications including GDM, PIH, preeclampsia and preterm delivery, even after adjustment for age and multiple pregnancies (Table 2). As for the neonatal complications, the birth weight, Apgar score at 1 and 5 min, admission to special baby care unit (SBCU) and admission to neonatal intensive care unit (NICU) were similar among the three groups (Table 3).
Discussion Many studies have reported on the obstetric and neonatal complications in women with PCOS, but there was paucity of data in the literature regarding the obstetric and neonatal
Women with PCOS and isolated polycystic ovaries
DOI: 10.3109/14767058.2014.921673
477
Table 1. Baseline characteristics. p value Control (n ¼ 174) PCOS (n ¼ 25) PCO (n ¼ 54) Overall PCOS versus control PCO versus control PCOS versus PCO
Group Age (years) BMI (kg/m2) Duration of infertility Primary subfertility
32.7 ± 3.1 21.5 ± 2.6 4.6 ± 2.7 115 (66.1)
31.4 ± 2 22.8 ± 3.6 3.9 ± 1.7 17 (68.0)
34.2 ± 2.8 21.2 ± 2.0 4.7 ± 2.8 39 (72.2)
50.001 NS NS NS
40.002
0.043
50.001
Data expressed as mean ± SD or n (%).
Table 2. Obstetrics complications.
J Matern Fetal Neonatal Med 2015.28:475-478. Downloaded from informahealthcare.com by Kainan University on 04/18/15. For personal use only.
Control (n ¼ 171) GDM (%) GHT (%) PET (%) IUGR (%) Preterm (%) Congenital abnormality (%)
52 6 7 11 42 12
(30.4) (3.5) (4.1) (6.5) (24.6) (7.5)
PCOS (n ¼ 24) 7 2 2 3 6 3
(29.2) (8.3) (8.3) (12.5) (25.0) (12.5)
PCO (n ¼ 53)
p value
16 (30.2) 0 1 (1.9) 6 (11.3) 8 (15.1) 0
NS NS (0.15) NS (0.41) NS (0.37) NS (0.34) NS (0.064)
Adjusted p value* NS NS NS NS NS NS
(0.99) (0.53) (0.38) (0.40) (0.24) (0.66)
*Adjusted for age and multiple pregnancy.
Table 3. Obstetrics outcomes.
Gestation at delivery (weeks) Birth weight (g) Apgar score at 1 min 55 (%) Apgar score at 5 min 57 (%) SCBU admission (%) NICU admission (%)
Control (n ¼ 171)
PCOS (n ¼ 24)
PCO (n ¼ 53)
37.2 ± 3.0 2701 ± 671 4 (3.1) 1 (0.8) 44 (32.1) 23 (16.8)
37.7 ± 2.4 2722 ± 628 0 0 6 (31.6) 2 (10.5)
37.6 ± 2.7 2737 ± 668 1 (2.8) 1 (2.9) 9 (25.7) 5 (14.3)
p value NS NS NS NS NS NS
(0.51) (0.98) (0.72) (0.51) (0.76) (0.76)
Adjusted p value* NS NS NS NS NS NS
(0.77) (0.64) (0.33) (0.20) (0.35) (0.26)
*Adjusted for age and multiple pregnancy.
outcomes of women with isolated PCO morphology. To our best knowledge, this was the first study to look at the perinatal outcome in women with isolated PCO, and to compare them with PCOS women and women with normal ovaries. In our study, we did not find a significant difference in the pregnancy and neonatal outcomes among women with PCOS, isolated PCO and the non-PCO controls after adjusting for age and multiple pregnancies. PCOS has been associated with negative pregnancy outcome but interpretation of previous studies has been limited by different study designs, inconsistent diagnostic criteria for PCOS and selection of the control group [8]. The negative impact was thought to be related to the metabolic abnormalities such as insulin resistance and hyperandrogenism in PCOS women, and therefore they had a tendency to develop GDM, PIH and preeclampsia. Sayin et al. [12] showed that some women with PCO shared some endocrine abnormalities with those with PCOS, but others have shown that ovulatory PCO women did not express similar abnormalities as PCOS women and that PCO might only represent some normal variation in the ovarian morphology [18]. Our study showed that both the PCOS and isolated PCO groups did not have adverse pregnancy and birth outcomes when compared with controls, and the results were consistent with studies focusing on PCOS women when age and weight were adjusted for [19]. Isolated PCO might be regarded as a normal variation of ovarian morphology, as suggested by a previous
study [18]. However, our study is limited by the fact that women with isolated PCO were not evaluated endocrinologically albeit having regular ovulatory cycle and no evidence of clinical hyperandrogenism. The inconsistence of our findings in PCOS group with those from previous meta-analyses may be explained by the fact that majority of our patients do not suffer from obesity and clinical hyperandrogenism, which were the two key features that were thought to be associated with adverse pregnancy outcomes. The mean BMI were 523 kg/m2 in each group and they were comparable among the three groups. This could possibly explain the similar prevalence of complications in the groups, as obesity is known to be a major risk factor associated with adverse pregnancy outcomes [20]. The world-wide prevalence of GDM ranges from 1% to 14% [21], depending on which population is being screened and which screening strategies and diagnostic criteria are used [22]. Our prevalence of 30% in all groups was relatively high compared to the world-wide figures, but comparable to our local data and consistent with other studies reporting higher prevalence in Asians [23,24]. Limitations of the study include the small sample size, the retrospective study design and the timing of selection of the age-matched controls. A better design would be using ageand weight-matched controls selected from women who had undergone their first prenatal ultrasound examination after successful IVF treatment rather than before IVF stimulation.
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Recent studies have looked at obstetric and neonatal outcomes in PCOS women with different phenotypes. These studies showed that increased risk for adverse obstetric and neonatal outcomes in patients with PCOS varies widely according to the different phenotypes and features of PCOS, with a higher incidence in hyperandrogenic PCOS women [9,25]. Our study is concordant with their findings that there was no significant effect on obstetric and neonatal outcomes for nonhyperandrogenic PCOS women (RR 0.54, 95% CI 0.09–1.63). In conclusion, our current study confirms that women with isolated PCO do not have an increased risk for adverse obstetric or neonatal outcomes, and it may be a normal variation of ovary morphology. Further studies with a larger sample size analyzing PCOS women according to different phenotypes would give us a better understanding on its significance.
Declaration of interest The authors report no declarations of interest.
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