Hum. Reprod. Advance Access published online on June 10, 2008
Human Reproduction, doi:10.1093/humrep/den136
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Fecundability and spontaneous abortions in women with self-reported oligo-amenorrhea and/or hirsutism: Northern Finland Birth Cohort 1966 Study
1 Family Federation of Finland, 90220 Oulu, Finland 2 Department of Obstetrics and Gynaecology, University Hospital of Oulu, Kajaanintie 52, 90029 Oulu, Finland 3 National Public Health Institute, 90220 Oulu, Finland 4 Institute of Reproductive and Developmental Biology, Imperial College London, London, UK 5 Department of Epidemiology and Public Health, Imperial College London, London, UK 6 Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK 7 Department of Clinical Chemistry, University Hospital of Oulu, 90029 Oulu, Finland 8 Department of Public Health Science and General Practice, University of Oulu, 90220 Oulu, Finland
9 Correspondence address. Tel: +358-8-3154109; Fax: +358-8 3154310; E-mail: lmp{at}cc.oulu.fi
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Abstract |
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BACKGROUND: Women with polycystic ovary syndrome (PCOS) suffer from anovulatory infertility and hospital-based studies suggest that they have an increased risk of spontaneous abortion. Our aim was to investigate the proportion of women, with self-reported oligo-amenorrhea and/or hirsutism in a general population, who had suffered from infertility, the percentage of them managing to conceive and their rate of spontaneous abortion.
METHODS: At age 31, a postal questionnaire including questions about hirsutism and oligo-amenorrhea was sent to all women from the population-based Northern Finland Birth Cohort 1966 (total n = 5889). Of these, 4535 (79.5%) answered the questionnaire, 1103 reported hirsutism and/or oligo/amenorrhea (symptomatic women) and 3420 were non-symptomatic. The fecundability ratio (FR) was defined as the probability of conception of a clinically detectable pregnancy within 12 months.
RESULTS: The overall pregnancy (77.7% versus 75.6%) and spontaneous abortion (19.3% versus 18.6%) rates did not differ between the two groups and the risk of spontaneous abortion was not associated with body mass index (BMI), waist-to-hip ratio (WHR) or waist circumference. Symptomatic women had suffered more often from infertility than non-symptomatic women (19.4% versus 11.1%, P < 0.01). Oligo-amenorrhea and/or hirsutism (FR = 0.74, P < 0.001) and obesity (FR = 0.68, P = 0.002) were both independently associated with decreased fecundability, but symptomatic women had become pregnant and had one or two successful deliveries as often as non-symptomatic women.
CONCLUSIONS: Women with self-reported oligo-amenorrhea and/or hirsutism had lower fecundability and suffered more often from infertility, but had at least one delivery as often as non-symptomatic women, and did not exhibit an increased risk of spontaneous abortion.
Key words: PCOS/spontaneous abortion/infertility/oligo-amenorrhea/hirsutism
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Introduction |
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Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. There is also evidence that women with PCOS have an increased spontaneous abortion risk compared with women without the syndrome (Sagle et al., 1988
; Regan et al., 1989; Balen et al., 1993; Watson et al., 1993; Clifford et al., 1994; Glueck et al., 2002, 2004). However, most of these studies have focused on hospital-based subjects, including women seeking infertility treatment and thus do not necessarily represent a general population. Even within a patient population, not all studies have shown an inappropriately high spontaneous abortion rate among women with PCOS. For example, spontaneous abortion rates in series of anovulatory patients with PCOS, treated with either clomiphene (Kousta et al., 1997) or low-dose follicle-stimulating hormone (White et al., 1996; Gorry et al., 2006), have been reported to be between 20% and 24%. Other reported series have also noted normal fecundity and spontaneous abortion rates in women with the syndrome (Dahlgren et al., 1992; Winter et al., 2002).
Obesity is common in PCOS, and almost all obese subjects with the syndrome have insulin resistance (Dunaif et al., 1987; Holte et al., 1994). Obesity and insulin resistance appear to have independent roles in the etiology of spontaneous abortions (Hamilton-Fairley et al., 1992; Wang et al.. 2002; Jakubowicz et al., 2004) and obesity per se seems to be an independent risk factor for spontaneous abortion after infertility treatments (Bruni et al., 2003; Bellver and Pellicer, 2004; Lashen et al., 2004).
In the present study, we take advantage of a large, representative cohort of women to study fecundability and risk of spontaneous abortion in women with self-reported oligo-amenorrhea and/or hirsutism.
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Materials and Methods |
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Study population
The population derives from the Northern Finland Birth Cohort 1966 (NFBC 1966) members followed from fetal life until the age of 31 years (Rantakallio, 1988
) (Fig. 1). In 1966, 5889 females were born alive. In 1997–1998, 5608 of these women were traced for the 31-year follow-up including a postal questionnaire with questions on socio-demographic and other health background factors, including pregnancies, infertility problems and treatments, and 4074 women were invited for a clinical examination. Of these, 3115 (76%) attended this clinical examination. This sample is fully representative of the original female cohort: neither birth nor early socio-demographic data differed materially between those attending clinical examination and the remainder of the women in the cohort (Jarvelin et al., 2004). Information on hirsutism and oligo-amenorrhea was inquired by the following questions: (i) is your menstrual cycle over twice a year more than 35 days? and (ii) do you have excessive growth of body hair? Of women who returned the questionnaire, with informed consent (n = 4535), 24% reported symptoms of hirsutism and/or oligo-amenorrhea; 10.6% reported hirsutism alone, 10.5% oligo-amenorrhea alone and 3.5% reported both symptoms.
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Subjects using oral contraceptives or hormonal intrauterine devices were excluded from the study (Fig. 1). From analyses concerning calculation of body mass index (BMI), women who were pregnant at the time that they filled in the questionnaire were excluded; and from the calculation of time to pregnancy (TTP) analysis (Wennborg et al., 2001
), those women without contraception, who had not tried to get pregnant, or those who were pregnant following contraceptive failure were excluded. Women who had never been pregnant were excluded from the spontaneous abortion analysis (Fig. 1).
BMI was calculated as the ratio of weight (kg) and height squared (m2) (values obtained from the clinical examination and, when lacking, from the questionnaire). Women were categorized into four groups by the criteria of WHO, underweight (BMI<18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2) and obese (
30.0 kg/m2). The waist-to-hip ratio (WHR) was measured at 31 years at the clinical examination (n = 3115), as the ratio between the circumferences of the waist (at the level midway between the lowest rib margin and the iliac crest) and the hip (at the widest trochanters).
Time to pregnancy (TTP) in months was measured from the beginning of unprotected intercourse until the first pregnancy. TTP measures were derived using questions and response options as shown in Table I. Infertility problems were defined as active exposure to pregnancy (i.e. not using contraception) for 1 year without getting pregnant.
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This study was approved by the ethical committee of the University of Oulu.
Statistical analyses
Student's two-tailed t-test and 
2 test were used for the descriptive parameters as appropriate.
TTP was used to estimate the fecundability, i.e. the probability of conception of a clinically detectable pregnancy within 12 months. Unadjusted survival curves for both non-symptomatic and symptomatic women, separately stratified by potential confounders, were used to analyze the effect of PCOS symptoms, BMI, WHR and waist circumference on TTP (categorized response variable). The analysis was stopped at 13 months, to avoid problems due to the possible effects of infertility treatments and because most women conceive within 12 months. The Cox logistic model for discrete survival times (STATA) was used to compute proportional FR (with 95% confidence intervals, CIs) between different groups.
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Results |
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Women with either symptom of PCOS (N = 437) had significantly higher BMI (25.1 versus 24.2 kg/m2, P < 0.001), WHR (0.82 versus 0.81, P = 0.002) and waist circumference (81.2 versus 78.8 cm, P < 0.01) than non-symptomatic women, as previously reported (Taponen et al., 2003
).
Fecundability
Both PCOS symptoms and obesity, but not overweight, were independently associated with decreased fecundability. Women reporting both hirsutism and oligo-amenorrhea had the lowest chance of conceiving within 12 months, 0.39 (95% CI 0.27–0.54); those with oligo-amenorrhea alone also had significantly reduced fecundability compared with non-symptomatic women, whereas hirsutism alone was not associated with decreased fecundability (Table II). Obese women with both hirsutism and oligo-amenorrhea had the lowest FR of all groups (0.33, 95% CI 0.16–0.68).
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When estimated from the fecundability ratios, the chance of becoming pregnant within 12 months was significantly lower in the obese women compared with the overweight women (Table II).
Infertility
Symptomatic women suffered significantly more often from infertility than non-symptomatic women (26.5% versus 17.1%, P < 0.01, Table III), and this difference was seen in all BMI groups except in the underweight group and was most significant in the obese group (37.7% versus 15.7%, P = 0.001). For those who had sought help for infertility (n = 107 women, 11 partners, 205 both), the main reason for infertility was attributable to the woman in 52.5% of the couples in PCOS group and in 26.3% in the non-symptomatic group (P < 0.0001).
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Spontaneous abortions
Symptomatic women had a similar cumulative incidence of at least one spontaneous abortion as non-symptomatic women (Table IV) and the number of spontaneous abortions/recurrent (
3) spontaneous abortions per woman did not differ between symptomatic and non-symptomatic women (number of spontaneous abortion per woman: 0.25 (mean) ± 0.02 (SEM) versus 0.29 ± 0.01, P = NS; percentage of recurrent spontaneous abortion per woman: 0.8% versus 1.4%, P = NS in symptomatic compared with non-symptomatic women, respectively). The risk of spontaneous abortion was not associated with the types of PCOS symptoms (Table V) nor BMI (spontaneous abortion rates 16.5% versus 18.5%, P = NS in symptomatic compared with non-symptomatic women with BMI > 27 kg/m2), WHR (if WHR < 0.85, spontaneous abortion rates 18.9% versus 17.7%, P = NS; if WHR > 0.85, 14.4% versus 18.1%, P = NS in symptomatic compared with non-symptomatic women, respectively), nor waist circumference (if waist < 80 cm, spontaneous abortion rates 20.3% versus 18.2%, P = NS; if waist > 80 cm, 13.7% versus 17.2%, P = NS in symptomatic compared with non-symptomatic women, respectively).
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Pregnancy rate and deliveries
Symptomatic women became pregnant at least once, as frequently as non-symptomatic women (Table VI), although the TTP was longer. Symptomatic women had also at least one successful pregnancy, leading to delivery, as often as non-symptomatic women. However, at the age of 31 year, women with both hirsutism and irregular menstruation had a smaller family size than non-symptomatic women or women with only one PCOS symptom (Table VI).
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Discussion |
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The present study suggests that women with self-reported oligo-amenorrhea and/or hirsutism did not display any increased risk of spontaneous abortion compared with non-symptomatic women. They had at least one birth as often as did the non-symptomatic women, but their family size was smaller at age 31 year. However, these women suffered more often from fertility problems and had significantly lower fecundability than non-symptomatic women. Obesity, commonly combined with PCOS, decreased fecundability significantly and independently among symptomatic women.
The strength of our study is that it is the first study of a large population based cohort of females followed longitudinally since fetal life (Rantakallio, 1988). In addition, it is by far the largest general population-based study in which a symptom based approach with information on both oligo-amenorrhea and hirsutism has been used to investigate associations between self-reported oligo-amenorrhea and/or hirsutism and clinical characteristics. However, a limitation of our study is that the diagnosis of PCOS was based on a questionnaire, suggesting some risk for information bias in reporting the symptoms. Nevertheless, we have previously shown that self-reported oligo-amenorrhea and hirsutism can help to identify most women with the typical endocrine profile of PCOS (Taponen et al., 2003, 2004). Moreover, women with both oligo-amenorrhea and hirsutism already fulfill the Rotterdam criteria for diagnosis of PCOS (Anonymous, 2004; Taponen et al., 2004).
As expected, oligo-amenorrhea was associated with decreased fecundability and the presence of both hirsutism and oligo-amenorrhea had the strongest adverse effect. In contrast, fecundability in women with only hirsutism did not differ significantly from the reference group. This may be explained by the fact that hirsutism is perhaps the most obviously subjective symptom and is influenced by differing perceptions of what constitutes excess body hair.
Women with only oligo-amenorrhea or who had both PCOS symptoms had infertility problems more frequently than non-symptomatic women, in all except in the underweight BMI group (data not shown). The underweight group may have been underpowered to see a significant difference. This result may be also due to an increased risk of anovulation due to hypogonadotrophic hypogonadism in this group of non-symptomatic women. Underweight women have previously been shown to suffer more often from infertility than normal weight women (Davies, 2006). As expected, the female factor was the most common reason for the infertility among symptomatic women.
Both PCOS symptoms and obesity, but not overweight, had independent and adverse effects on fecundability, and women suffering from both obesity and PCOS symptoms experienced the lowest fecundability. Our results are in line with previous findings showing that obese women with PCOS have the greatest difficulties in conceiving (Pasquali et al., 2006). Moreover, the attributable risk calculation indicated that the possibility of conceiving within 12 months could improve by one-third if the BMI would decrease from obese to overweight (although we did not have longitudinal data to confirm this), strengthening the importance of losing weight to reduce the need for infertility treatment, as shown in numerous studies of obese women (Clark et al., 1998; Hoeger et al., 2004; Norman et al., 2004).
To our knowledge, this is the first population-based study exploring the risk of spontaneous abortion among women with self-reported oligo-amenorrhea and/or hirsutism compared with non-symptomatic women. We found no increased risk of spontaneous abortion or recurrent spontaneous abortion among women with self-reported oligo-amenorrhea and/or hirsutism, in contrast to most previous studies suggesting a 2–5-fold increased risk of spontaneous abortion among women with PCOS compared with control population. However, these studies had small numbers of patients and were performed in totally different selected groups of women with proper PCOS diagnosis attending infertility centers or spontaneous abortion clinics, also suggesting a hospital attendance bias (Sagle et al., 1988; Balen et al., 1993; Watson et al., 1993; Glueck et al., 2004).
Obesity has been shown to increase spontaneous abortion rates in the general population (Hamilton-Fairley et al., 1992), and some data suggest that an elevated spontaneous abortion risk is connected only to obesity and not to the diagnosis of PCOS (Wang et al., 2002). In contrast, in the present study, neither obesity nor even abdominal obesity increased the spontaneous abortion risk. This is in line with one study conducted in women treated by in vitro fertilization, also including very early spontaneous abortions, and showing no significant association between early pregnancy loss and obesity. In that study, the effect of abdominal obesity on early spontaneous abortion rate was not investigated and the diagnosis of PCOS increased the risk of spontaneous abortion slightly but not significantly from 15% to 26% (Winter et al., 2002). One explanation for our finding may be that the subjects were at a relatively young age, before the manifestation of the adverse effects of obesity and age on insulin sensitivity and metabolic factors. The follow-up of these women in the future at the age of 45 years will reveal whether these results remain unchanged throughout the reproductive years.
Women with both PCOS symptoms were less likely to have more than two children than women with only one symptom and non-symptomatic women. However, it was comforting to observe that symptomatic women, as well as the women with both symptoms, gave birth successfully as often as non-symptomatic women and had at least 1–2 children, in agreement with previously published data (Dahlgren et al., 1992). Moreover, this result may also suggest that fecundability can be restored by infertility treatment, which is an important issue as regards the prognosis of infertility treatment in this particular group of women.
We conclude that women with self-reported oligo-amenorrhea and/or hirsutism have lower fecundability and more frequent infertility problems than non-symptomatic women in a general population sample, but did not exhibit an increased risk of spontaneous abortion. Obesity decreased fecundability significantly and independently. Despite a smaller family size, these women had one or two deliveries as often as non-symptomatic women.
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Author's Contribution |
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R.K.: (i) Substantial contributions to conception and design, and analysis and interpretation of data, (ii) drafting the article and revising it critically for important intellectual content and (iii) final approval of the version to be published.
A.P.: (i) Substantial contributions to conception and design, acquisition of data, and analysis and interpretation of data, (ii) drafting the article and revising it critically for important intellectual content and (iii) final approval of the version to be published.
S.F.: (i) Substantial contributions to analysis and interpretation of data, (ii) drafting and revising the article critically for important intellectual content and (iii) final approval of the version to be published.
H.M.: (i) Substantial contributions to analysis and interpretation of data, (ii) revising the article critically for important intellectual content and (iii) final approval of the version to be published.
U.S.: (i) Substantial contributions to analysis and interpretation of data, (ii) drafting the article and revising it critically for important intellectual content and (iii) final approval of the version to be published.
A-L.H.: (i) Substantial contributions to conception and design, acquisition of data, and analysis and interpretation of data, (ii) revising the article critically for important intellectual content and (iii) final approval of the version to be published.
M.I.M.: (i) Substantial contributions to analysis and interpretation of data, (ii) revising the article critically for important intellectual content and (iii) final approval of the version to be published.
A.R.: (i) Substantial contributions to conception and design, (ii) drafting the article or revising it critically for important intellectual content and (iii) final approval of the version to be published.
M-R.J.: (i) Substantial contributions to conception and design and acquisition of data, (ii) revising the article critically for important intellectual content and (iii) final approval of the version to be published.
L.M-P.: (i) Substantial contributions to conception and design, and analysis and interpretation of data, (ii) drafting the article and revising it critically for important intellectual content and (iii) final approval of the version to be published.
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Funding |
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Academy of Finland (9/2006 nro 1114194).
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References |
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Anonymous. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod (2004) 19:41–47.
Balen AH, Tan SL, MacDougall J, Jacobs HS. Miscarriage rates following in-vitro fertilization are increased in women with polycystic ovaries and reduced by pituitary desensitization with buserelin. Hum Reprod (1993) 8:959–964.
Bellver J, Pellicer A. Impact of obesity on spontaneous abortion. Am J Obstet Gynecol (2004) 190:293–294.[Web of Science][Medline]
Bruni V, Dei M, Pontello V, Vangelisti P. The management of polycystic ovary syndrome. Ann N Y Acad Sci (2003) 997:307–321.[CrossRef][Web of Science][Medline]
Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod (1998) 13:1502–1505.
Clifford K, Rai R, Watson H, Regan L. An informative protocol for the investigation of recurrent miscarriage: preliminary experience of 500 consecutive cases. Hum Reprod (1994) 9:1328–1332.
Dahlgren E, Johansson S, Lindstedt G, Knutsson F, Oden A, Janson PO, Mattson LA, Crona N, Lundberg PA. Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating hormones. Fertil Steril (1992) 57:505–513.[Web of Science][Medline]
Davies MJ. Evidence for effects of weight on reproduction in women. Reprod Biomed Online (2006) 12:552–561.[Web of Science][Medline]
Dunaif A, Graf M, Mandeli J, Laumas V, Dobrjansky A. Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia. J Clin Endocrinol Metab (1987) 65:499–507.
Glueck CJ, Wang P, Goldenberg N, Sieve-Smith L. Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin. Hum Reprod (2002) 17:2858–2864.
Glueck CJ, Wang P, Goldenberg N, Sieve L. Pregnancy loss, polycystic ovary syndrome, thrombophilia, hypofibrinolysis, enoxaparin, metformin. Clin Appl Thromb Hemost (2004) 10:323–334.
Gorry A, White DM, Franks S. Infertility in polycystic ovary syndrome: focus on low-dose gonadotropin treatment. Endocr Rev (2006) 30:27–33.[CrossRef]
Hamilton-Fairley D, Kiddy D, Watson H, Paterson C, Franks S. Association of moderate obesity with a poor pregnancy outcome in women with polycystic ovary syndrome treated with low dose gonadotrophin. Br J Obstet Gynaecol (1992) 99:128–131.[Web of Science][Medline]
Hoeger KM, Kochman L, Wixom N, Craig K, Miller RK, Guzick DS. A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study. Fertil Steril (2004) 82:421–429.[CrossRef][Web of Science][Medline]
Holte J, Bergh T, Berne C, Berglund L, Lithell H. Enhanced early insulin response to glucose in relation to insulin resistance in women with polycystic ovary syndrome and normal glucose tolerance. J Clin Endocrinol Metab (1994) 78:1052–1058.[Abstract]
Jakubowicz DJ, Essah PA, Seppala M, Jakubowicz S, Baillargeon JP, Koistinen R, Nestler JE. Reduced serum glycodelin and insulin-like growth factor-binding protein-1 in women with polycystic ovary syndrome during first trimester of pregnancy. J Clin Endocrinol Metab (2004) 89:833–839.
Jarvelin MR, Sovio U, King V, Lauren L, Xu B, McCarthy MI, et al. Early life factors and blood pressure at age 31 years in the 1966 northern Finland birth cohort. Hypertension (2004) 44:838–846.
Kousta E, White DM, Franks S. Modern use of clomiphene citrate in induction of ovulation. Hum Reprod Update (1997) 3:359–365.
Lashen H, Fear K, Sturdee DW. Obesity is associated with increased risk of first trimester and recurrent miscarriage: matched case-control study. Hum Reprod (2004) 19:1644–1646.
Norman RJ, Noakes M, Wu R, Davies MJ, Moran L, Wang JX. Improving reproductive performance in overweight/obese women with effective weight management. Hum Reprod Update (2004) 10:267–280.
Pasquali R, Gambineri A, Pagotto U. The impact of obesity on reproduction in women with polycystic ovary syndrome. BJOG (2006) 113:1148–1159.[CrossRef][Web of Science][Medline]
Rantakallio P. The longitudinal study of the northern Finland birth cohort of 1966. Paediatr Perinat Epidemiol (1988) 2:59–88.[Medline]
Regan L, Braude PR, Trembath PL. Influence of past reproductive performance on risk of spontaneous abortion. BMJ (1989) 299:541–545.
Sagle M, Bishop K, Ridley N, Alexander FM, Michel M, Bonney RC, Beard RW. Recurrent early miscarriage and polycystic ovaries. BMJ (1988) 297:1027–1028.
Taponen S, Martikainen H, Jarvelin MR, Laitinen J, Pouta A, Hartikainen AL, Sovio U, McCarthy MI, Franks S, Ruokonen A. Hormonal profile of women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland birth cohort 1966 study. J Clin Endocrinol Metab (2003) 88:141–147.
Taponen S, Ahonkallio S, Martikainen H, Koivunen R, Ruokonen A, Sovio U, Hartikainen AL, Pouta A, Laitinen J, King V, et al. Prevalence of polycystic ovaries in women with self-reported symptoms of oligomenorrhoea and/or hirsutism: Northern Finland Birth Cohort 1966 Study. Hum Reprod (2004) 19:1083–1088.
Wang JX, Davies MJ, Norman RJ. Obesity increases the risk of spontaneous abortion during infertility treatment. Obes Res (2002) 10:551–554.[Web of Science][Medline]
Watson H, Kiddy DS, Hamilton-Fairley D, Scanlon MJ, Barnard C, Collins WP, Bonney RC, Franks S. Hypersecretion of luteinizing hormone and ovarian steroids in women with recurrent early miscarriage. Hum Reprod (1993) 8:829–833.
Wennborg H, Bodin L, Vainio H, Axelsson G. Solvent use and time to pregnancy among female personnel in biomedical laboratories in Sweden. Occup Environ Med (2001) 58:225–231.
White DM, Polson DW, Kiddy D, Sagle P, Watson H, Gilling-Smith C, Hamilton-Fairley D, Franks S. Induction of ovulation with low-dose gonadotropins in polycystic ovary syndrome: an analysis of 109 pregnancies in 225 women. J Clin Endocrinol Metab (1996) 81:3821–3824.
Winter E, Wang J, Davies MJ, Norman R. Early pregnancy loss following assisted reproductive technology treatment. Hum Reprod (2002) 17:3220–3223.
Submitted on December 18, 2007; resubmitted on March 18, 2008; accepted on April 1, 2008.
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