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Biomedical subjects

Hannu Martikainen

Publications and source records attributed to Hannu Martikainen.

13 recordsLinked to original sources

A randomized study comparing efficacy and patient satisfaction in medical or surgical treatment of miscarriage.

OBJECTIVE: To compare the efficacy of the medical treatment to surgical uterine evacuation and patient satisfaction in each group. DESIGN: A randomized, controlled study. SETTING: An outpatient clinic in the Department of Gynecology and Obstetrics in Oulu University Hospital, Oulu, Finland. PATIENT(S): Ninety-eight eligible women who had had miscarriages. INTERVENTION(S): Medical treatment of miscarriage (n = 49) with 200 mg of mifepristone and 0.8 mg of misoprostol 1-3 days after the event or surgical uterine evacuation (n = 49). Questionnaires to collect data of experienced pain and patient satisfaction. MAIN OUTCOME MEASURE(S): The complete abortion rate with the primary treatment (primary outcome) and the patient satisfaction (secondary outcome). RESULT(S): The success rate was equal (100% in surgical and 90% in medical group). More infections were diagnosed in the surgical group. Surgically treated patients were more satisfied with the treatment (100% vs. 88%). Medical treatment was considered more painful and fewer patients (70% vs. 91%) would choose the medical method in the future. CONCLUSION(S): Medical treatment is an effective alternative to surgical treatment and increases the choice available to women. Surgical treatment is associated with more infections. More medically treated patients experienced pain and dissatisfaction.

Abortifacient Agents, Nonsteroidal↗

Elective single embryo transfer in women aged 36-39 years.

BACKGROUND: The elective single embryo transfer policy is the only effective strategy known to minimize the risk of multiple pregnancy. However, little is known about its applicability to women older than 35 years. METHODS: Analysis was carried out on 1224 fresh IVF/ICSI cycles with embryo transfer and 828 frozen embryo transfer (FET) cycles of women aged 36-39 years. In the fresh cycles, 335 elective single top quality embryo (eSET), 110 elective single non top quality embryo (nt-eSET), 194 compulsory single embryo (cSET) and 585 double embryo transfers (DET) were carried out. RESULTS: Pregnancy rate/embryo transfer (33.1 versus 29.9%) and live birth rate (26.0 versus 21.9%) in fresh cycles did not differ significantly between the eSET and the DET groups. However, women in the eSET group had a higher cumulative pregnancy rate (54.0% versus 35.0%) and a higher cumulative live birth rate (41.8% versus 26.7%, P < 0.0001) compared with those in the DET group. The cumulative multiple birth rate in the eSET group was 1.7%, whereas in the DET group it was 16.6% (P < 0.0001). CONCLUSIONS: The eSET policy can be applied also to patients aged 36-39 years, reducing the risk of multiple birth and increasing the safety of assisted reproduction technique (ART) in this age group.

Adult↗

Analysis of multiple data sets reveals no association between the insulin gene variable number tandem repeat element and polycystic ovary syndrome or related traits.

CONTEXT: Variation at the insulin gene VNTR (variable number tandem repeat) minisatellite has been reported to be associated with polycystic ovary syndrome (PCOS), but findings have been inconsistent and all studies have featured small sample sizes. OBJECTIVE: To gain a robust understanding of the role of the INS-VNTR in PCOS susceptibility. DESIGN: Case-control, family-based association and quantitative trait analyses. SETTING AND PARTICIPANTS: A UK population comprising 255 parent-offspring trios, 185 additional cases, and 1062 control subjects (cases and controls all British/Irish) as well as 1599 women from a northern Finland population-based birth cohort characterized for PCO symptomatology and testosterone levels. VNTR class was inferred from genotyping of the -23HphI variant. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): INS-VNTR genotype frequencies between subject groups, body mass index, and testosterone levels by genotype. RESULTS: Case-control analyses in both UK and Finnish samples failed to confirm previously reported class III allele associations with PCOS (UK, P = 0.43, Finnish, P = 0.31; Kruskal-Wallis chi2). Transmission analysis in trios showed no excess transmission of either allele (P = 0.62), regardless of parent of origin (maternal: P = 0.73; paternal: P = 0.66). No association between genotype and testosterone levels was seen in any sample (UK PCOS subjects, P = 0.95; Finnish symptomatic cases, P = 0.38; Finnish control women, P = 0.58). CONCLUSIONS: Despite the strong biological candidacy and supportive data from previous studies, we conclude that variation at the INS-VNTR has no major role in the development of PCOS.

Adult↗

An initial low response predicts poor outcome in in vitro fertilization/intracytoplasmic sperm injection despite improved ovarian response in consecutive cycles.

OBJECTIVE: To study the predictive value of initial low response (LR) in IVF/intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective analysis. SETTING: Two Finnish fertility centers. PATIENT(S): A total of 3,846 IVF/ICSI cycles performed from 1994 to 2002. INTERVENTION(S): Consecutive cycles in the same subject were identified. The study groups consisted of subjects who had three treatment cycles and at least one LR cycle (n = 80). MAIN OUTCOME MEASURE(S): Pregnancy rate (PR), total gonadotropin dose, and embryo quality. RESULT(S): Only 2.5% (2/80) of subjects had a LR in all three consecutive cycles. In 43 women an initial LR was followed by >/=1 normal response (NR) cycle, and in 35 women an initial NR was followed by >/=1 LR cycle. The PR/cycle was similarly low in women with an initial LR and an initial NR (10.1% vs. 16.2%). An increase in gonadotropin dose resulted in a higher number of oocytes in women with an initial LR (from 2.1 +/- 0.9 to 6.7 +/- 2.7) but the PR/cycle remained low, compared to the overall mean PR (27.2%). In cycles in which top quality embryos were transferred, subjects with an initial LR had a lower PR than women with an initial NR (17.8% vs. 41.2%). CONCLUSION(S): An initial LR is a predictor of poor outcome in subsequent cycles, even if ovarian response is improved by increasing the gonadotropin dose or a top quality embryo is replaced.

Adult↗

Day 2 elective single embryo transfer in clinical practice: better outcome in ICSI cycles.

BACKGROUND: Single embryo transfer (SET) after IVF/ICSI has been shown to result in an acceptable pregnancy rate in selected subjects. In our unit, SET is routinely carried out among women under the age of 36 in the first or second treatment cycle when a top-quality embryo is available. In order to define further the selection criteria for SET, we have analysed the outcome of elective SET (eSET), including the cumulative pregnancy rate after frozen embryo transfers, performed in the years 2000-2002 in the Oulu Fertility Center. METHODS: During the study period, a total of 1271 transfers were performed, and in 468 cycles SET (39% of all transfers) was carried out. Of the SET cycles, in 308 cases a top-quality embryo was transferred on day 2 and extra embryos were frozen. Of these eSET cycles, ICSI was carried out in 87 cycles (28%). RESULTS: The overall clinical pregnancy rate per transfer was 34.7% in the eSET cycles. In the eSET ICSI cycles, the clinical pregnancy rate was significantly higher than in the corresponding IVF cycles (50.6 versus 28.5%, P < 0.001). The cumulative pregnancy rate per patient after fresh and frozen embryo transfers was also significantly higher after ICSI (71.2 versus 53.4%, P < 0.01). CONCLUSIONS: A high cumulative pregnancy rate per oocyte retrieval can be achieved after eSET in daily clinical practice. The implantation rate of fresh top-quality embryos in the ICSI cycles was significantly higher than in the IVF cycles, possibly due to more successful selection of the embryo for embryo transfer on day 2 after ICSI. In addition, our data suggest that embryo quality is a more important determinant of outcome than the age of the woman.

Adult↗

Large-scale analysis of the relationship between CYP11A promoter variation, polycystic ovarian syndrome, and serum testosterone.

CYP11A, the gene encoding p450scc, a key enzyme in steroid biosynthesis, is a strong biological candidate for polycystic ovary syndrome (PCOS) susceptibility. Four of the five published studies that have examined CYP11A for evidence of linkage and/or association have reported significant relationships with polycystic ovary (PCO) status and/or serum testosterone levels. However, study sizes have been modest, and the current study aimed to reevaluate these findings using significantly larger clinical resources. A pair of CYP11A promoter microsatellites, including the pentanucleotide (D15S520) previously implicated in trait susceptibility, were genotyped in 371 PCOS patients of United Kingdom origin, using both case-control and family-based association methods, and in 1589 women from a population-based birth cohort from Finland characterized for PCO symptomatology and testosterone levels. Although nominally significant differences in allele and genotype frequencies at both loci were observed in the United Kingdom case-control study (for example, an excess of the pentanucleotide four-repeat allele in cases, P = 0.005), these findings were not substantiated in the other analyses, and no discernable relationship was seen between variation at these loci and serum testosterone levels. These studies indicate that the strength of, and indeed the existence of, associations between CYP11A promoter variation and androgen-related phenotypes has been substantially overestimated in previous studies.

Adult↗

Metabolic cardiovascular disease risk factors in women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland Birth Cohort 1966 Study.

The metabolic cardiovascular disease (CVD) risk factors of women with self-reported oligomenorrhea and/or hirsutism, which are symptoms of polycystic ovary syndrome (PCOS), were investigated in a general population-based Northern Finland Birth Cohort 1966 Study to determine whether women with PCOS symptoms at 31 yr would be distinguishable from asymptomatic controls in terms of CVD risk factors. A total of 518 cases with oligomenorrhea and/or hirsutism and 1036 randomly selected controls were analyzed. C-Reactive protein (CRP; median, 0.70 vs. 0.60 mg/liter; P = 0.026), triglycerides (mean, 0.97 vs. 0.91 mmol/liter; P = 0.039), body mass index (BMI; mean, 25.1 vs. 24.2 kg/m(2); P < 0.001), and waist/hip ratio (mean, 0.82 vs. 0.81; P = 0.001) were significantly higher, and high-density lipoprotein cholesterol levels were lower (mean, 1.60 vs. 1.66 mmol/liter; P = 0.002) in the cases compared with the controls. Total cholesterol, low-density lipoprotein cholesterol, and blood pressure showed no statistically significant differences between the cases and the controls. In terms of metabolic CVD risk factors, women reporting hirsutism alone were indistinguishable from the control group, and those who reported both oligomenorrhea and hirsutism had the most severe changes in risk factor profiles. Because obesity is strongly related to PCOS symptoms, the analyses were stratified by BMI. After stratification into normal weight (BMI, <25 kg/m(2)), overweight (25 kg/m(2) or=30 kg/m(2)) groups, the waist/hip ratio was significantly higher among the overweight cases (mean, 0.84 vs. 0.83; P = 0.04). Among the obese women, high-density lipoprotein cholesterol was significantly lower (mean, 1.32 vs. 1.48 mmol/liter; P = 0.002) among the cases, and triglycerides tended to be higher (mean, 1.43 vs. 1.27 mmol/liter; P = 0.068) than in controls. In conclusion, these results indicate that self-reported symptoms of oligomenorrhea and/or hirsutism, particularly in the presence of both symptoms, may be helpful to identify women with metabolic cardiovascular risk factor accumulation associated with PCOS.

Adult↗

Variation at the insulin gene VNTR (variable number tandem repeat) polymorphism and early growth: studies in a large Finnish birth cohort.

Variation at the insulin gene (INS-)VNTR (variable number of tandem repeats) minisatellite polymorphism has been reported to be associated with both early growth and adult metabolic phenotypes. However, the samples studied have been small and the relationship between INS-VNTR variation and parameters of early growth inconsistent, with four previous studies producing conflicting results. We have studied the relationship between INS-VNTR class (measured by genotyping the nearby -23HphI variant with which it is in tight linkage disequilibrium) and early growth in 5,646 members of the Northern Finnish Birth Cohort of 1966. Comparing class III homozygotes with other genotypes using multivariate linear regression analysis, we found no significant associations with any early growth measure (birth weight, birth length, ponderal index, and head circumference at 1 year), even after stratifying subjects by growth trajectory during infancy and/or birth order. For example, among infants with limited postnatal growth realignment (n = 2,470), class III/III infants were no heavier at birth (difference [+/-SE] in the means [fully adjusted], 58 +/- 51 g; P = 0.26) than class I/- infants. No significant associations were detected following reanalysis with an additive model (for example, for birth weight, beta = 20 g [95% CI -3 to 44], P = 0.09). Studies of this large population-based cohort have failed to generate convincing evidence that INS-VNTR variation influences early growth.

Birth Order↗

Hormonal profile of women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland birth cohort 1966 study.

The hormonal profiles of nested female patients (n = 500) with self-reported symptoms typical of polycystic ovary syndrome (PCOS), oligomenorrhea, and/or hirsutism and their randomly selected controls (n = 1026) at the age of 31 yr were analyzed in a general population-based Northern Finland birth cohort 1966 to find out whether the symptomatic women also have the endocrine characteristics of PCOS and could be detected in a general population using simple questions. Higher medians of serum testosterone (T) (2.10 vs. 1.90 nmol/liter, P < 0.001), LH (5.40 vs. 4.85 U/liter, P = 0.005), insulin (53.8 vs. 51.66 pmol/liter, P = 0.040), and free androgen index (FAI) (4.01 vs. 3.03, P < 0.001) and lower glucose/insulin ratio (91.1 x 10(8) vs. 94.9 x 10(8), P = 0.048) and SHBG (52.4 vs. 60.7 nmol/liter, P < 0.001) were observed among the cases, but no difference was observed in cortisol and glucose levels between the cases and controls. Of all the women in the cohort, 10.2% reported only oligomenorrhea and had biochemical findings similar to the whole case group. Those who reported only hirsutism (10.4%) were in between the case and control groups according to biochemical findings. The subjects who reported both oligomenorrhea and hirsutism (3.4%) had the highest T, LH, FAI, insulin, and glucose and the lowest SHBG and glucose/insulin ratio, compared with the case group and the groups with either symptom only indicating a dose-response manner in typical endocrine profile of PCOS by adding up symptoms. The levels of T and FAI were higher and SHBG lower in groups with overweight or obesity both at 14 and 31 yr, compared with groups with normal weight at 14 yr and overweight or obesity at 31 yr. In the group with normal weight at 14 and 31 yr and the group with overweight or obesity at 14 yr but normal weight at 31 yr, the levels of T and FAI were lowest and SHBG highest. T and FAI were higher and SHBG lower among the cases than the controls in groups stratified by weight development from adolescence to adulthood. In conclusion, this longitudinal study of a large, stable population indicates that women with self-reported symptoms of hirsutism and/or oligomenorrhea show endocrine characteristics of PCOS and can be detected in a general population using simple questions. These symptoms are markers of the underlying metabolic alterations possibly associated with increased health risks in later life.

Adult↗

Metformin versus ethinyl estradiol-cyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: a randomized study.

Metformin, an insulin-sensitizing drug, has been shown to improve ovarian function and glucose metabolism in obese women with polycystic ovary syndrome (PCOS), but its effects and possible benefits in nonobese PCOS subjects are not well known. Seventeen nonobese (body mass index < 25 kg/m(2)) women with PCOS were randomized to receive either metformin (500 mg twice daily for 3 months, then 1000 mg twice daily for 3 months; n = 8) or ethinyl estradiol (EE, 35 microg)-cyproterone acetate (CA, 2 mg) oral contraceptive pills (EE-CA; n = 9). Waist to hip ratio; serum concentrations of sex steroids, glucose, and insulin during a 75-g oral glucose tolerance test; early phase insulin and C-peptide secretion; and insulin sensitivity using a euglycemic hyperinsulinemic clamp were assessed at baseline and at 3 and 6 months of treatment. Metformin did not have any effect on glucose tolerance or insulin sensitivity, but fasting insulin concentrations decreased from 44.4 +/- 5.1 (SE) to 29.8 +/- 4.3 pmol/liter (P = 0.03), the waist to hip ratio decreased from 0.78 +/- 0.01 to 0.75 +/- 0.01 (P = 0.01), and hepatic insulin clearance increased during the treatment. Furthermore, metformin decreased serum testosterone levels from 2.7 +/- 0.3 to 2.0 +/- 0.2 nmol/liter (P = 0.01) and improved menstrual cyclicity. EE-CA did not have any significant effect on glucose tolerance, serum insulin levels, or insulin sensitivity, but it increased slightly the body mass index (P = 0.09) and significantly serum leptin concentrations (P < 0.001) and decreased serum testosterone levels from 2.1 +/- 0.2 to 1.4 +/- 0.2 nmol/liter (P = 0.03). In conclusion, EE-CA seems to be an efficient mode of therapy for hyperandrogenic symptoms associated with PCOS, but its possible negative effects on insulin and glucose metabolism also have to be taken into consideration in nonobese subjects. Metformin improved hyperandrogenism, hyperinsulinemia, and menstrual cyclicity, most likely through its positive effect on insulin clearance and abdominal adiposity. Thus, similarly to obese PCOS women, nonobese PCOS subjects with anovulation may also benefit from metformin treatment.

Adult↗

The degree of difficulty of embryo transfer is an independent factor for predicting pregnancy.

BACKGROUND: The role of embryo transfer as regards the success of IVF/ICSI treatments is recognized but has not been comprehensively evaluated. In order to determine its importance, the degree of difficulty of 4807 embryo transfers after IVF/ICSI was analysed retrospectively. METHODS: Logistic regression analysis identified the age of the subject, type of treatment (IVF versus ICSI), number of embryos transferred and degree of difficulty of embryo transfer as independent factors predicting pregnancy. The main focus of the study was to evaluate the importance of the difficulty of embryo transfer after taking into account the other confounding variables. RESULTS: Embryo transfer was classified as easy (2821), intermediate (1644) or difficult (342). The transfer was considered difficult if it was time consuming, the catheter met great resistance, there was a need to change the catheter, if sounding or cervical dilatation was needed or if blood was found in any part of the catheter. Easy or intermediate transfers resulted in a 1.7-fold higher pregnancy rate than difficult transfers (P < 0.0001; 95% confidence interval: 1.3-2.2). CONCLUSIONS: This study demonstrates that the degree of difficulty of embryo transfer is an independent factor as regards achieving pregnancy after IVF/ICSI. All efforts should be made to avoid difficult embryo transfers. Physicians should be alert to the factors associated with embryo transfer and should be instructed to use a stepwise approach in difficult transfers.

Catheterization↗

The course of pregnancy and delivery and the use of maternal healthcare services after standard IVF in Northern Finland 1990-1995.

BACKGROUND: The objective of this study was to evaluate the course of pregnancy and delivery and the use of maternal healthcare after IVF. METHODS: This population-based cohort study included all women who had undergone IVF treatment in Northern Finland leading to delivery in 1990-1995 (n = 225) and control pregnancies derived from the Finnish Medical Birth Register (n = 671) matched for sex of the child, year of birth, area, maternal age, parity, social class and fetal plurality. The analyses were stratified by plurality. Outcome measures were pregnancy complications, mode of delivery, gestational length and the level of use of antenatal care. RESULTS: The results showed an increased risk for vaginal bleeding throughout pregnancy [relative risk (RR) 4.1, 95% confidence interval (CI) 2.5-6.7 for singletons; RR 6.9, 95% CI 2.5-19.2 for twins], threatened preterm birth (RR 1.8, 95% CI 1.1-2.9, singletons) and intrahepatic cholestasis of pregnancy (RR 3.8, 95% CI 1.0-15.0, singletons) in IVF pregnancies, as well as an increase in the use of specialized antenatal care. CONCLUSIONS: IVF pregnancies following standard, fresh ova IVF treatments are at greater risk of obstetric problems than spontaneously conceived pregnancies, and hence IVF mothers use more specialized antenatal care than others. The pregnancy complications after IVF are likely to be due to maternal characteristics regarding infertility and to a high incidence of multiple pregnancies.

Adult↗