Hormone profiling, including anti-Müllerian hormone (AMH), for the diagnosis of polycystic ovary syndrome (PCOS) and characterization of PCOS phenotypes.

Objective was to evaluate serum anti-Müllerian hormone (AMH) levels in polycystic ovary syndrome (PCOS) and in its different phenotypes in relation to clinical, endocrine and metabolic parameters using a new automated VIDAS® method and to compare it with the Gen II method. Study design was multi-center study including 319 PCOS women and 109 healthy controls. Serum AMH levels measured using VIDAS® were significantly higher in PCOS women than controls (p < .001), and they correlated with those measured using the AMH Gen II method. An AMH cutoff value of 42.1 pmol/L distinguished PCOS women from controls with 67% sensitivity and 83% specificity. The PCOS women with three Rotterdam criteria or hyperandrogenism displayed significantly higher AMH levels compared with those with two Rotterdam criteria or normoandrogenism. In PCOS, AMH levels correlated positively with luteinizing hormone (LH), androgen and sex hormone-binding globulin (SHBG) levels and negatively with BMI, abdominal obesity, follicle-stimulating hormone (FSH), fasting glucose and insulin, and insulin resistance. In conclusion, AMH evaluated using the VIDAS® method distinguished PCOS patients from healthy controls relatively well, especially in those with more severe phenotypes. Further studies are needed to establish whether AMH measurements can distinguish PCOS patients with different metabolic risk factors.

Ovarian tissue cryopreservation and transplantation among alternatives for fertility preservation in the Nordic countries - compilation of 20 years of multicenter experience.

INTRODUCTION: The aim of this study is to report the current status of ovarian tissue cryopreservation among alternatives for fertility preservation in the Nordic countries. MATERIAL AND METHODS: A questionnaire was sent to 14 Nordic academic reproductive centers with established fertility preservation programs. It covered fertility preservation cases performed up to December 2014, standard procedures for ovarian tissue cryopreservation and oocyte cryopreservation and reproductive outcomes following ovarian tissue transplantation. RESULTS: Among the Nordic countries, Denmark and Norway practice ovarian tissue cryopreservation as a clinical treatment (822 and 164 cases, respectively) and their programs are centralized. In Sweden (457 cases), ovarian tissue cryopreservation is practiced at five of six centers and in Finland at all five centers (145 cases). Nearly all considered ovarian tissue cryopreservation to be experimental. In Iceland, embryo cryopreservation is the only option for fertility preservation. Most centers use slow-freezing methods for ovarian tissue cryopreservation. Most patients selected for ovarian tissue cryopreservation were newly diagnosed with cancer and the tissue was predominantly retrieved laparoscopically by unilateral oophorectomy. Only minor complications were reported. In total, 46 women have undergone ovarian tissue transplantation aiming at recovering fertility, 17 healthy children have been born and several additional pregnancies are currently ongoing. Whenever patients' clinical condition is permissive, oocyte cryopreservation after hormonal stimulation is preferred for fertility preservation. Between 2012 and 2014, a smaller proportion of females have undergone fertility preservation in the Nordic centers, in comparison to males (1:3). CONCLUSIONS: Overall, ovarian tissue cryopreservation was reported to be safe. Slow freezing methods are still preferred. Promising results of recovery of fertility have been reported in Nordic countries that have initiated ovarian tissue transplantation procedures.

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.

[Infertility and risk of cancer]. / Lapsettomuus ja syöpäriski.

Ovulation problems, ovarian endometriosis and impaired sperm quality may be factors underlying infertility and possibly predisposing to cancer diseases. Infertility therapies utilize products that alter the hormonal balance and may in theory increase the risk of cancer. Handling of gametes in the laboratory is also likely to influence gene regulation. Ovulation induction therapies may increase the risk of uterine cancer, and in vitro fertilization (IVF) therapies may increase ovarian tumors. Children born after IVF therapies seem to have a statistically elevated risk of cancer. Instead of risk ratios, the use of clear figures is recommended in patient information.

Preinterventional quantitative magnetic resonance imaging predicts uterus and leiomyoma size reduction after uterine artery embolization.

PURPOSE: To investigate the relationship between magnetic resonance imaging (MRI) measures and uterus and leiomyoma size reductions after uterine artery embolization (UAE). MATERIALS AND METHODS: Fifty-two women with leiomyomas underwent selective UAEs. Uterine and dominant leiomyoma sizes were measured with preinterventional MRI and a 6-month follow-up MRI. Four MRI measures of the dominant leiomyoma were recorded: T1 time; T2 time; leiomyoma-to-skeletal muscle T2 SI-ratio; and percentage of contrast enhancement. To evaluate the predictive value of MRI measures we used Spearman rank correlation, area under the receiver operating characteristic (ROC) curve (A(z)), and values for diagnostic performance. RESULTS: Uterus and dominant leiomyoma size reductions were highly variable. Leiomyoma size reductions of >or=75% were accurately predicted with leiomyoma-to-skeletal muscle T2 SI-ratio (ROC curve A(z) = 0.930; 95% confidence interval [CI]: 0.853, 1.000). Leiomyoma size reductions >or=75% were predicted by leiomyoma-to-skeletal muscle T2 SI-ratio >or=3.5 and T1-time >or=750 msec with 100% and 86% sensitivities and 67% and 72% specificities, respectively. Uterus size reduction >or=50% were identified by dominant leiomyoma-to-skeletal muscle T2 SI-ratio >or=2.5. CONCLUSION: Uterus and dominant leiomyoma size reductions after UAE were predicted with preoperative MRI measures of the dominant leiomyoma.

Uterine artery embolisation versus hysterectomy for leiomyomas: primary and 2-year follow-up results of a randomised prospective clinical trial.

OBJECTIVE: To compare uterine artery embolisation (UAE) and hysterectomy for the treatment of leiomyomas at 2-year follow-up in a prospective, randomised, single-centre study. METHODS: Fifty-seven symptomatic patients were randomised to UAE (n = 27) or hysterectomy (n = 30). Complications, recovery, reinterventions and satisfaction with treatment were recorded. Primary endpoint was improvement of symptoms. Analyses were performed by intent-to-treat and per protocol. RESULTS: Two hysterectomy patients (7%) developed major complications. Hospital discharge occurred earlier after UAE than after hysterectomy (p < 0.001). Length of sick leave was longer after hysterectomy than after UAE (p < 0.001). Twenty-two (82%) UAE patients and 28 (93%) hysterectomy patients reported overall relief of symptoms (p = 0.173). In 12/18 (67%) UAE patients menorrhagia was completely resolved or reduced. Improvement of pressure symptoms was reported significantly more by UAE patients than by hysterectomy patients (19/20 [95%] versus 18/26 [69%], respectively; p = 0.029). Five (19%) UAE patients underwent additional interventions due to worsening symptoms. Twenty-four (89%) UAE patients and 29 (97%) hysterectomy patients would have chosen treatment again (p = 0.336). CONCLUSION: UAE gave relief of symptoms (apart from menorrhagia) comparable to hysterectomy with less severe complications, but with an increased rate of secondary interventions. UAE may be the preferable treatment especially for patients with pressure symptoms.

Cumulative baby take-home rate among women with PCOS treated by IVF.

OBJECTIVE: This study was designed to evaluate cumulative live birth rates after an in vitro fertilisation (IVF) programme in polycystic ovary syndrome (PCOS) women. SUBJECTS AND METHODS: IVF outcomes of 66 women with PCOS diagnosed via Rotterdam criteria, who failed to conceive after ovulation induction, were compared with 106 women with tubal factor infertility. One hundred and twenty-five cycles were analysed in the PCOS group and 225 cycles in the control group (1-4 cycles per woman). Results of frozen-thawed cycles, occurrence of ovarian hyperstimulation syndrome (OHSS) and drop-outs were also included. RESULTS: Despite a lower pregnancy rate among women with PCOS versus controls, the cumulative baby take-home rate did not differ between the groups (48.5% and 44.3%). The first cycle was the most successful cycle for living birth rate in PCOS group. One-third of PCOS women, who did not continue after unsuccessful treatment, had more miscarriage but not more OHSS compared to those who continued. CONCLUSIONS: Although the baby take-home rate was similar among women with PCOS, and controls, the outcomes of consecutive cycles were not equal. Cumulative data give more realistic information than pooled cycles.

[Obstetric and gynecologic embolizations]. / Obstetriset ja gynekologiset embolisaatiot: synnytyksenjälkeisen verenvuodon tukkimisesta myoomaembolisaatioon.

Postpartum embolization to decrease the maternal mortality rate and postpartum hysterectomies. An interventional radiologist performs the embolization at the obstetrician's request, when conventional means have failed to stop the bleeding. This will efficiently stop the bleeding. Fertility appears to remain normal after embolization. Embolization of uterine arteries is also utilized for the treatment of symptomatic myomas in patients, who do not wish to become pregnant. After the embolization the myomas will gradually shrink within months. The procedure has been found to be safe.

Pain after uterine fibroid embolisation is associated with the severity of myometrial ischaemia on magnetic resonance imaging.

The purpose of the study was to evaluate uterine ischaemia after uterine artery embolisation (UAE) using magnetic resonance imaging and the role of myometrial and fibroid ischaemia in the pathogenesis of post-procedural pain. T1-weighted gradient echo imaging before and after contrast agent was performed on 62 women before and 24 h after UAE. We assessed the severity (mild, moderate, severe) of myometrial ischaemia, and the percentage and volume of ischaemic tissue in myometrium and fibroids. The Verbal Rating Scale was used to assess in-hospital post-procedural pain (1-3 mild, 4-6 moderate, 7-10 severe). Mean maximal pain was 7.7. Myometrial ischaemia was mild, moderate and severe in 29, 23 and 10 patients, respectively. Moderate or severe myometrial ischaemia (p = 0.041), the percentage (p = 0.037) and volume (p = 0.012) of ischaemic tissue in the myometrium, and a large volume of embolic material (p = 0.038) correlated with severe pain. In summary, pain following UAE is common and partly explained by myometrial ischaemia.

Androgen receptor gene CAG repeat length in women with metabolic syndrome.

OBJECTIVE: The length of the androgen receptor gene CAG repeat [AR (CAG)(n)] modulates the activity of the androgen receptor (AR), and this polymorphism has been shown to modulate body fat mass and serum concentrations of insulin in men. We hypothesized that shorter AR (CAG)(n) is associated with metabolic syndrome (MBS) or its components in women. DESIGN, PATIENTS AND MEASUREMENTS: In a cross-sectional controlled study we studied 52 Finnish women aged 34-55 years with MBS and 69 age-matched controls. All participants were recruited from a sample of women drawn from the Finnish population register. We compared the mean AR (CAG)(n) in the two groups. Furthermore, we correlated the AR (CAG)(n) with serum testosterone, androstenedione, dehydroepiandrosterone sulfate and several parameters of glucose and lipid metabolism in each group and in all 121 women. RESULTS: There was no difference in the biallelic mean AR (CAG)(n) between the MBS and the control group (21.6+/-0.2 vs. 21.8+/-0.2, not significant). The AR (CAG)(n) did not correlate significantly with any of the clinical or biochemical parameters of glucose or fat metabolism. However, it correlated negatively with serum testosterone (-0.195, p = 0.04) and androstenedione concentrations (-0.205, p = 0.03) in all studied women. CONCLUSIONS: The AR (CAG)(n) is not a major determinant of MBS in women but it contributes to ovarian androgen production.

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).

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.

Outcome of assisted reproductive technology (ART) and subsequent self-reported life satisfaction.

OBJECTIVE: To compare life satisfaction between women with successful or unsuccessful outcome after assisted reproductive treatment (ART) by taking into account the time since the last ART. DESIGN: Cohort study. SETTING: Tertiary hospital. PATIENTS: A total of 987 consecutive women who had undergone ART during 1996-2007 were invited and altogether 505 women participated in the study. INTERVENTIONS: A postal enquiry with a life satisfaction scale. MAIN OUTCOME MEASURE: Self-reported life satisfaction in respect to the time since the last ART. RESULTS: In general, women who achieved a live birth after ART had a significantly higher life satisfaction than those who had unsuccessful ART, especially when compared in the first three years. The difference disappeared in the time period of 6-9 years after ART. The unsuccessfully treated women who had a child by some other means before or after the unsuccessful ART had comparable life satisfaction with successfully treated women even earlier. CONCLUSIONS: Even if unsuccessful ART outcome is associated with subsequent lower level of life satisfaction, it does not seem to threaten the long-term wellbeing.

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 infertility's 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.

Association between magnetic resonance imaging findings of uterine leiomyomas and symptoms demanding treatment.

PURPOSE: To evaluate the association between magnetic resonance imaging (MRI) derived uterine and leiomyoma characteristics and symptoms demanding treatment. MATERIALS AND METHODS: Consecutive patients (n=122; mean age, 47.5 years) with symptomatic leiomyomas participated in a prospective study. The leiomyoma/endometrium relationship, sizes of leiomyomas and uteri, and number and enhancement of leiomyomas were determined by MRI. Submucosal leiomyomas were classified as protruding either ≥50% or <50% into the uterine cavity. RESULTS: Sixty-nine patients (57%) had menorrhagia and pressure symptoms, while 26 (21%) had only menorrhagia and 27 (22%) pressure symptoms alone. Leiomyomas with ≥50% protrusion into the uterine cavity were detected more often in patients with both symptoms or just menorrhagia than in those with pressure symptoms only (18/69 [26%] versus 1/27 [4%], P=0.013; 10/26 [39%] versus 1/27 [4%], P=0.002, respectively). The degree of enhancement of leiomyomas was higher (P=0.005) and leiomyomas were smaller (P=0.002) in patients with menorrhagia than in those with pressure symptoms. Large uterine and leiomyoma measures were associated with increased urinary frequency (P values 0.002-0.032). Urinary stress incontinence, abdominal pain, and pressure on the back were not associated with MRI findings. CONCLUSION: In comparison with pressure symptoms, menorrhagia is associated with smaller uterine and leiomyoma size and with more intense enhancement. While a submucosal leiomyoma largely protruding into the cavity contributes to menorrhagia, significance of a minor submucosal component seems to be unclear. The large leiomyoma and uterine volumes contribute to increased urinary frequency, whereas other mechanisms for urinary stress incontinence and pain symptoms should be considered.

Metformin improves pregnancy and live-birth rates in women with polycystic ovary syndrome (PCOS): a multicenter, double-blind, placebo-controlled randomized trial.

BACKGROUND: The role of metformin in the treatment of infertility in women with polycystic ovary syndrome (PCOS) is still controversial. OBJECTIVE AND OUTCOMES: We investigated whether metformin decreases the early miscarriage rate and improves the pregnancy rates (PR) and live-birth rates (LBR) in PCOS. METHODS: This was a multicenter, randomized (1:1), double-blind, placebo-controlled study. Three hundred twenty women with PCOS and anovulatory infertility were randomized to metformin (n = 160, Diformin; obese women, 1000 mg two times daily; nonobese subjects, 500 mg + 1000 mg daily) or identical doses of placebo (n = 160). After 3 months' treatment, another appropriate infertility treatment was combined if necessary. If pregnancy occurred, metformin/placebo was continued up to the 12th week. RESULTS: Miscarriage rates were low and similar in the two groups (metformin 15.2% vs. placebo 17.9%, P = 0.8). Intent-to-treat analysis showed that metformin significantly improved PR and LBR (vs. placebo) in the whole study population (PR: 53.6 vs. 40.4%, P = 0.006; LBR: 41.9 vs. 28.8%, P = 0.014) and PR in obese women (49.0 vs. 31.4%, P = 0.04), and there was a similar trend in nonobese (PR: 58.6 vs. 47.6%, P = 0.09; LBR: 46.7 vs. 34.5%, P = 0.09) and in obese women with regard to LBR (35.7 vs. 21.9%, P = 0.07). Cox regression analysis showed that metformin plus standard infertility treatment increased the chance of pregnancy 1.6 times (hazard rate 1.6, 95% confidence interval 1.13-2.27). CONCLUSION: Obese women especially seem to benefit from 3 months' pretreatment with metformin and its combination thereafter with routine ovulation induction in anovulatory infertility.

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.

Assessment of attitudes towards assisted reproduction: a survey among medical students and parous women.

BACKGROUND: The present paper explores attitudes towards different aspects of assisted reproductive technologies among parous women and future doctors (third- and fourth-year medical students). METHODS: We anonymously surveyed 200 parous women who had at least three infants and had given birth at Kuopio University Hospital, and 200 medical students of Kuopio University. RESULTS: The overall response rate was 45%. Most of the medical students were childless (95.7%), unmarried (63.8%), and younger (24 vs. 35 years) compared with the parous women (p < 0.001). Medical students were liberal in questions of who has the right to get infertility treatment: 49% of them would allow the possibility to lesbian couples, 43% to homosexual couples and over 50% to single women. Over 40% of medical students would allow the use of a surrogate mother for lesbian and homosexual couples; the number was under 20% in the group of parous women. Their setting of priorities within the field of reproductive health also showed differences in prostate cancer screening, doctor's appointments for contraception, abortion and menopausal hormone replacement therapy. CONCLUSIONS: Medical students take a rather liberal stance on reproductive issues. On the other hand, baseline attitudes among medical students reveal some degree of subjectivism when it comes to allocation of scarce healthcare resources within the field of reproductive health. Medical education faces a challenge in ensuring that future physicians are able to set priorities and balance resources between preventive medicine and management of specific medical conditions, and to base their attitudes on evidence.