Maritta Hippeläinen

The androgenic sex hormone profile is an essential feature of metabolic syndrome in premenopausal women: a controlled community-based study

OBJECTIVE To evaluate sex hormones in premenopausal white women with metabolic syndrome (MBS). DESIGN Cross-sectional controlled community-based study. SETTING Pieksämäki District Health Center, Pieksämäki, Finland. PATIENT(S) Five hundred forty-three women, aged 34 to 54 years, were screened according to National Cholesterol Education Program criteria: waist >88 cm, hypertension >/=130/>/=85 mm Hg, hypertriglyceridemia >/=1.7 mmol/L, high-density lipoprotein (HDL)-cholesterol <1.3 mmol/L, and fasting glucose >/=6.1 mmol/L. Sixty-three women fulfilled at least three of the above-mentioned criteria and were enrolled. Eighty-eight age-matched women without MBS served as controls. INTERVENTION(S) None. MAIN OUTCOME MEASURES Sex steroid levels in relation to insulin sensitivity and body composition. RESULT(S) A markedly lower insulin sensitivity index and higher free androgen index were detected in the women with MBS than in the controls. Abdominal obesity and increased diastolic blood pressure were significantly associated with high free androgen index in multiple regression analysis. CONCLUSION(S) A hyperandrogenic hormone profile appeared to be a typical feature of premenopausal female MBS even without polycystic ovary syndrome (PCOS).

Child rate, pregnancy outcome and ovarian function in females with classical 21‐hydroxylase deficiency

Background. Ovulatory disorders and decreased fertility rates have been found in females with classical 21‐hydroxylase deficiency (21‐OHD). We analyzed the pregnancies of 29 females with classical 21‐hydroxylase deficiency and examined 16 of these women in a cross‐sectional study.

Pituitary gonadal axis and child rate in males with classical 21-hydroxylase deficiency.

Though appropriate glucocorticoid substitution therapy should abolish both cortisol deficiency and adrenal androgen excess in patients with 21-hydroxylase deficiency (21-OHD), the longterm outcome is not always satisfactory. There are several reports on low adult height in both male and female patients, and impaired fertility has been reported in females with 21-OHD. There are only few reports on gonadal function of adult male patients with 21-OHD. In this study, we calculated the child rate of all the 29 diagnosed adult Finnish males with classical 21-OHD and compared it with the mean child rate of the whole Finnish male population with equal age distribution. Sixteen males with 21-OHD and their age-matched healthy controls were further examined in a cross-sectional study. Auxology and pituitary gonadal axis were examined in both patients and controls. Testicular ultrasonography of the patients was also performed. The mean child rate of the 29 males with 21-OHD was 0.07 which was significantly lower (p<0.001) than that in the Finnish male population of the same age (0.34). In the cross-sectional study, males with 21-OHD had serum testosterone, inhibin B, LH and FSH concentrations comparable to those of healthy controls and reference values. Serum DHEA-S concentrations were remarkably low, even in the undersubstituted males with 21-OHD (p<0.001, compared with the healthy controls). In the patient group, serum inhibin B concentration did not correlate with serum FSH concentration. Adrenal rest tumors of the testicles were found in two undersubstituted males with 21-OHD. In conclusion, our study suggests normal pituitary and gonadal function but reduced child rate in adult males with 21-OHD. This might be explained by suboptimal psychosocial adaptation to the chronic disease. However, the patients in this study were young and the final child rate may become essentially higher.

Comparison of the pregnancy outcomes of subfertile women after infertility treatment and in naturally conceived pregnancies

BACKGROUND Adverse obstetric outcomes in pregnancies achieved through assisted reproductive technology (ART) could either be due to the technology or to the underlying subfertility or to both. To address this issue, we compared the pregnancy outcomes of singletons conceived naturally after a long time to pregnancy (TTP) with those of ART pregnancies. METHODS We analysed an existing birth database. Altogether 428 ART pregnancies were compared with 928 spontaneously conceived pregnancies with TTP of 2 years or more, during the period 1989-2007 at Kuopio University Hospital, Finland. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for pregnancy outcomes. RESULTS Between treated and untreated subfertile women no significant differences were found in the rates of Caesarean sections (OR 1.21, 95% CI 0.89-1.64), preterm births (OR 1.28, 95% CI 0.81-2.03), small for gestational age (SGA) birthweight (OR 0.95, 95% CI 0.65-1.39), need of neonatal intensive care (OR 1.28, 95% CI 0.88-1.88) or low Apgar scores (OR 1.19, 95% CI 0.47-3.04). However, compared with pregnancies of women with TTP 0-6 months, ART pregnancies had significantly increased risks of preterm or very preterm birth, low birthweight and need of neonatal intensive care. CONCLUSIONS The risks of preterm birth, SGA, need for neonatal intensive care and low Apgar scores were not significantly different between subfertile women who conceived spontaneously and those who conceived through ART indicating that maternal factors relating to subfertility and not only infertility treatment are associated with adverse pregnancy outcomes.

Obstetric Outcome in Women with Endometriosis – A Matched Case-Control Study

Background: Immunological deficiencies, altered angiogenic activity, infiltrative potential and growth factors are plausible factors behind endometriosis. The aim of this study was to determine whether endometriosis interferes with the course or outcome of pregnancy. Study Design: In this matched case-control study, we analyzed obstetric outcome among 137 women with endometriosis and 137 controls matched as regards IVF procedures and parity who gave singleton births at Kuopio University Hospital between January 1994 and December 2000. In affected women, the diagnosis was histologically verified, whereas the controls were eligible for the study only if they had undergone laparoscopy/tomy in connection with tubal sterilization, or infertility unrelated to endometriosis. Results: No statistically significant differences were detected in reproductive risk factors in women with endometriosis, with the exception of mean maternal age (31.2 years in the cases vs. 34 years in the controls). The mean birth weight (±SD) among those delivering at term (>37 completed weeks) was 3,600 (±542) g in the control group and 3,547 (±456) g in the study group. Placental weight was comparable in both groups. Overall pregnancy characteristics and pregnancy outcome measures were similar in women affected by endometriosis when compared with the control group. Conclusions: Any potential negative effect of endometriosis on obstetric outcome was undetectable.

Adverse Outcomes of IVF/ICSI Pregnancies Vary Depending on Aetiology of Infertility

In vitro fertilization (IVF) is a risk factor for pregnancy, but there have been few studies on the effect of infertilitys aetiology. Thus, we have assessed the role of aetiology on IVF pregnancy outcomes in a retrospective cohort study comparing the outcomes of IVF singleton pregnancies with those of spontaneous pregnancies in the general Finnish population. The study group consisted of 255 women with births resulting from singleton IVF pregnancies. Six subgroups were formed according to the following causes of infertility: anovulation (27%), endometriosis (19%), male factor (17%), tubal factor (15%), polycystic ovary syndrome (11%), and unexplained infertility (12%). The reference group consisted of 26,870 naturally conceived women. Adjusted odds ratios (AORs), for confounding factors such as age and parity, were estimated using logistic regression analysis. Women with endometriosis and anovulation had increased risks of preterm birth (AOR 3.25, 95% CI 1.5–7.1 and AOR 2.1, and 95% CI 1.0–4.2, resp.), while women in couples with male factor infertility had a twofold risk of admission to neonatal intensive care (AOR 2.5, 95% CI 1.2–5.3). The findings show that the aetiology of infertility influenced the obstetrics outcome, and that pooling results may obscure some increased risks among subgroups.

Associations between two single nucleotide polymorphisms in the adiponectin gene and polycystic ovary syndrome.

In the present study we determined whether genetic variability in the gene encoding adiponectin is associated with polycystic ovary syndrome (PCOS). Altogether 143 Caucasian women with PCOS and 245 healthy controls were genotyped for two single nucleotide polymorphisms (SNPs) in exon 2 and intron 2 in the adiponectin gene. Single-point analysis was expanded to pair-of-loci haplotype analysis to examine the estimated haplotype frequencies of the two SNPs, of unknown phase, in the PCOS and control groups. Estimated haplotype frequencies were assessed using the maximum-likelihood method, employing an expectation-maximization algorithm. A significantly different allele distribution in intron 2 SNP was observed between the groups, with the T allele being significantly reduced in the PCOS group (25.9%) compared with the control group (32.7%) ( p = 0.047), at an odds ratio of 0.72 (95% confidence interval 0.52–0.99). Otherwise, the allele and genotype distributions in either SNP were not statistically different between the groups. In haplotype estimation analysis, there was a lower frequency of the haplotype T–T in the PCOS group (25.9%) than in the control group (32.7%) ( p = 0.058). We conclude that polymorphisms of the adiponectin gene may be implicated in individual susceptibility to PCOS.

Prolonged time to pregnancy is associated with a greater risk of adverse outcomes

Births with known time to pregnancy (TTP) during the period 1989-2007 (n=17,114) were analyzed to investigate associations between TTP and pregnancy outcome among couples that conceived spontaneously. The adjusted odds ratio (95% confidence interval) for poor neonatal health, including low Apgar score, low umbilical vein pH, and need for neonatal intensive care, was 1.51 (1.09-2.09) in women who had a TTP of 25-36 months and 1.60 (1.18-2.19) in women who had a TTP of >or=37 months compared with women with a TTP of 0-6 months.

Experience of in vitro fertilization surrogacy in Finland

Background.  In vitro fertilization (IVF) surrogacy makes it possible for women who do not have a functional uterus to have their own genetic offspring. We describe here our experience of IVF surrogacy in Finland over a 10‐year period.

Two exonic single nucleotide polymorphisms in the microsomal epoxide hydrolase gene are associated with polycystic ovary syndrome

OBJECTIVE To determine whether genetic variability in the gene encoding microsomal epoxide hydrolase (EPHX) contributes to individual differences in susceptibility to the development of polycystic ovary syndrome (PCOS). DESIGN Retrospective case-control study. SETTING University-based clinic. PATIENT(S) One hundred twelve white women with PCOS and 115 healthy controls. INTERVENTION(S) None. MAIN OUTCOME MEASURES The presence of two single nucleotide polymorphisms (SNPs), T-->C (Tyr113His) in exon 3 and A-->G (His139Arg) in exon 4, in the EPHX gene. Single point analysis was expanded to pair of loci haplotype analysis to examine the estimated haplotype frequencies of the two SNPs, of unknown phase, in the PCOS and control groups. Estimated haplotype frequencies were assessed using the maximum-likelihood method, using an expectation-maximization algorithm. RESULT(S) Single point allele and genotype distributions in exon 3 and exon 4 of the EPHX gene were not statistically different between the groups. However, according to the haplotype estimation analysis, we observed a significantly elevated frequency of haplotype C-G (His113-Arg139) in the PCOS group versus the control group. The odds ratio for PCOS associated with the low activity haplotype C-G (His113-Arg139) was 2.28 (95% confidence interval 1.1-4.8). CONCLUSION(S) The use of two intragenic single nucleotide polymorphisms jointly in haplotype analysis of association demonstrated that the genetically determined low activity haplotype C-G (His113-Arg139) was significantly associated with PCOS.