Magnetic resonance guided high intensity focused ultrasound for uterine fibroids and adenomyosis has no effect on ovarian reserve.

INTRODUCTION: Uterine fibroids are the most common benign tumors in healthy women. High Intensity Focused Ultrasound (HIFU) is a modern, noninvasive thermal ablation method for treating uterine fibroids. There is increasing evidence that ultrasound guided HIFU (US-HIFU) has no adverse impact on ovarian reserve but little data exists on magnetic resonance guided HIFU (MR-HIFU). There are different options to estimate ovarian reserve, perhaps the most reliable being the measurement of serum Anti-Müllerian hormone (AMH). MATERIAL AND METHODS: Seventy-four (74) premenopausal women with serum AMH 0.1 ug/L or over, aged 24-48 and with fibroids or adenomyosis treated with MR-HIFU were enrolled in our study. AMH levels were analyzed before and 3 months after the MR-HIFU treatment. Correlations between AMH level changes and position of fibroids, fibroid volume, non-perfused volume ratio, and treatment energies were studied. RESULTS: The median AMH level before the HIFU treatment was 1.20 (range: 0.1-7.75 ug/L) and after the treatment 1.23 (range: 0.1-8.51 ug/L). No significant change was detected (p = .90). The patients were divided in three subgroups depending on the baseline AMH levels. The changes were not significant in any of the subgroups. Neither did the location of the treated fibroid affect the change of AMH levels nor the total energy used during treatment. CONCLUSIONS: MR-HIFU does not compromise the ovarian reserve. Neither the location of the treated fibroid nor the total energy used during MR-HIFU had any effect on the change of AMH levels.

Histological findings in resected leiomyomas following MR-HIFU treatment, single-institution data from seven patients with unfavorable focal therapy.

PURPOSE: Magnetic resonance - high-intensity focused ultrasound (MR-HIFU) is a noninvasive treatment option for symptomatic uterine leiomyomas. Currently, pretreatment MRI is used to assess tissue characteristics and predict the most likely therapeutic response for individual patients. However, these predictions still entail significant uncertainties. The impact of tissue properties on therapeutic outcomes remains poorly understood and detailed knowledge of the histological effects of ultrasound ablation is lacking. Investigating these aspects could aid in optimizing patient selection, enhancing treatment effects and improving treatment outcomes. METHODS AND MATERIALS: We present seven patients who underwent MR-HIFU treatment for leiomyoma followed by second-line surgical treatment. Tissue samples obtained during the surgery were stained with hematoxylin and eosin, Masson's trichrome and Herovici to evaluate general morphology, fibrosis and collagen deposition of leiomyomas. Immunohistochemical CD31, Ki-67 and MMP-2 stainings were performed to study vascularization, proliferation and matrix metalloproteinase-2 protein expression in leiomyomas, respectively. RESULTS: The clinical characteristics and radiological findings of the leiomyomas prior to treatment as well as qualitative histological findings after the treatment are presented and discussed in the context of current literature. A tentative model for volume reduction is presented. CONCLUSION: These findings provide insights into potential factors contributing to suboptimal therapeutic outcomes and the variability in histological changes following treatment.

Top-quality embryo transfer is associated with lower odds of ectopic pregnancy.

INTRODUCTION: The incidence of ectopic pregnancy is up to four times higher after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) than in spontaneous pregnancies, and the risk of ectopic pregnancy is increased by tubal factor infertility and the transfer of multiple embryos. However, the effect of embryo quality on the probability of ectopic pregnancy has not been investigated until now and it is not clear whether ovarian stimulation parameters affect the incidence of ectopic pregnancy. MATERIAL AND METHODS: An historical cohort study of 15 006 clinical pregnancies (diagnosed by ultrasound at 6-8 gestational weeks) after non-donor IVF/ICSI with fresh embryo transfer (n = 8952) or frozen-thawed embryo transfer (n = 6054). Treatments were performed during 2000-2017 in Finland. A total of 9207 (61.4%) single and 5799 (38.6%) double embryo transfers of no more than one top-quality embryo were evaluated. We analyzed the effects of multiple factors on ectopic pregnancy by logistic regression, including type of cycle (fresh vs frozen embryo transfer), female age, number and quality of embryos transferred, tubal factor infertility and factors of ovarian response to gonadotropin stimulation. RESULTS: Ectopic pregnancy was observed in 2.3% of cycles. There was no significant difference in ectopic pregnancy rate after fresh embryo transfer and frozen embryo transfer (2.2% vs 2.4%, p = 0.3). The ectopic pregnancy rate was lower in cycles with top-quality embryo transfer (1.9%) than of those where only non-top quality embryos were transferred (2.7%, p < 0.0001). Tubal factor infertility was diagnosed more often in ectopic pregnancy than in intrauterine pregnancies (21.2% vs 11.0%, p < 0.0001). Logistic regression revealed lower odds for ectopic pregnancy after a top-quality embryo transfer than after transfer of a non-top quality embryo (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.56-0.92, p = 0.007). Transfer of two vs one embryo (OR 1.35, 95% CI 1.05-1.70, p = 0.02) and tubal factor infertility (OR 2.21, 95% CI 1.68-2.91, p < 0.0001) significantly increased the risk of ectopic pregnancy. CONCLUSIONS: Transfer of non-top quality embryos is associated with a higher rate of ectopic pregnancy. This is particularly important to keep in mind in treatments with only non-top embryos available even in the absence of tubal factor infertility. To minimize the risk of ectopic pregnancy, the number of embryos transferred should be as low as possible.

Oestrogen therapy for postpartum depression: efficacy and adverse effects. A double-blind, randomized, placebo-controlled pilot study.

BACKGROUND: Postpartum depression (PPD) is detrimental to the mother and the family as a whole. Early initiation of appropriate treatment is important. The aim of this pilot study was to evaluate the efficacy and adverse effects of oestradiol treatment. METHODS: We performed a pilot double-blind, randomized, placebo-controlled study. Major depression was diagnosed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), and the severity of depression was evaluated using the Edinburgh Postnatal Depression Scale (EPDS). The duration of treatment with sublingual oestradiol hemihydrate (1-3 mg/day) was 12 weeks. RESULTS: The treatment group consisted of 16 mothers and the placebo group of 14 mothers. Thirteen mothers in the treatment group and ten in the placebo group recovered from depression during the treatment period as measured with the EPDS (<10). There was no evidence to suggest that oestradiol was more effective than placebo. More mothers in the treatment group than in the placebo group (eight vs. one) received gestagen treatment for irregular bleeding. Oestradiol did not disturb breastfeeding. The mean number of other adverse effects per mother was lower in the treatment group, and these were mostly somatic symptoms. CONCLUSION: Our findings warrant further studies on oestrogen therapy for PPD with and without antidepressant and gestagen therapy, and on adverse effects (including effects on vaginal bleeding and breastfeeding).

Maternal risk factors for congenital limb deficiencies: A population-based case-control study.

BACKGROUND: Risk factors for congenital limb deficiencies are poorly understood. OBJECTIVE: To investigate risk factors for congenital limb deficiencies. METHODS: We conducted a nationwide population-based case-control (1:5) study in Finland, using national registers on congenital anomalies, births, and induced abortions, cross-linked with data on maternal prescription medicine use obtained from the registers on Reimbursed Drug Purchases and Medical Special Reimbursements. Five hundred and four children with limb deficiencies (241 isolated, 181 syndromic, and 82 other associated anomalies) were identified, and 2,520 controls were matched to cases on residence and year of pregnancy. Non-syndromic cases (n = 323) were subdivided into longitudinal (n = 120), transverse (n = 123), intercalary (n = 24), mixed (n = 18), and unknown (n = 38) deficiencies. RESULTS: Pregestational diabetes was associated with all limb deficiencies (adjusted odds ratio [OR] 12.71, 95% confidence interval [CI] 2.37, 68.25) and with isolated (OR 11.42, 95% CI 2.00, 64.60) deficiencies. Primiparity was associated with increased risk of congenital limb deficiencies among all cases (OR 1.49, 95% CI 1.15, 1.93), isolated cases (OR 1.46, 95% CI 1.09, 1.96), and among cases with longitudinal (OR 1.90, 95% CI 1.24, 2.90) and transverse deficiencies (OR 1.75, 95% CI 1.13, 2.70). Young maternal age (<25 years) was associated with all congenital limb deficiencies (OR 1.40, 95% CI 1.02, 1.90) and transverse deficiencies (OR 1.76, 95% CI 1.05, 2.96). Advanced maternal age (≥35 years) was associated with syndromic (OR 1.82, 95% CI 1.19, 2.78) and transverse deficiencies (OR 1.94, 95% CI 1.06, 3.57). Maternal antiepileptic medication was associated with all (OR 5.77, 95% CI 1.75, 19.04) and with isolated cases (OR 3.83, 95% CI 1.02, 14.34). CONCLUSIONS: It is important that pregnant women taking medications, especially antiepileptics, or women with pregestational diabetes are carefully monitored with regard to the occurrence and risk of limb deficiencies in the fetus.

Feasibility of T2 relaxation time in predicting the technical outcome of MR-guided high-intensity focused ultrasound treatment of uterine fibroids.

PURPOSE: The aim of this study was to assess the feasibility of T2 relaxation time in predicting the immediate technical outcome i.e., nonperfused volume ratio (NPVr) of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) treatment of symptomatic uterine fibroids and to compare it with existing T2-weighted imaging methods (Funaki classification and scaled signal intensity, SSI). MATERIALS AND METHODS: 30 patients with 32 uterine fibroids underwent an MRI study including a quantitative T2 relaxation time measurement prior to MRgHIFU treatment. T2 relaxation times were measured with a multi-echo fast imaging-based technique with 16 echoes. The correlation between pretreatment values of the uterine fibroids and treatment outcomes, that is nonperfused volume ratios (NPVr), was assessed with nonparametric statistical measures. T2 relaxation time-based method was compared to existing T2-weighted imaging-based methods using receiver-operating-characteristics (ROC) curve analysis and Chi-square test. RESULTS: Nonparametric measures of association revealed a statistically significant negative correlation between T2 relaxation time values and NPVr. The T2 relaxation time classification (T2 I, T2 II, and T2 III) resulted in the whole model p-value of 0.0019, whereas the Funaki classification resulted in a p-value of 0.56. The T2 relaxation time classification (T2 I and T2 II) achieved a whole model of a p-value of 0.0024, whereas the SSI classification had a p-value of 0.0749. CONCLUSIONS: A longer T2 relaxation time of the fibroid prior to treatment correlated with a lower NPVr. Based on our results, the T2 relaxation time classifications seem to outperform the Funaki classification and the SSI method.

Feasibility of apparent diffusion coefficient in predicting the technical outcome of MR-guided high-intensity focused ultrasound treatment of uterine fibroids - a comparison with the Funaki classification.

PURPOSE: To investigate the feasibility of using an apparent diffusion coefficient (ADC) classification in predicting the technical outcome of magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU) treatment of symptomatic uterine fibroids and to compare it to the Funaki classification. MATERIALS AND METHODS: Forty-two patients with forty-eight uterine fibroids underwent diffusion-weighted imaging (DWI) before MRgHIFU treatment. The DW images were acquired with five different b-values. Correlations between ADC values and treatment parameters were assessed. Optimal ADC cutoff values were determined to predict technical outcomes, that is, nonperfused volume ratios (NPVr) such that three classification groups were created (NPVr of <30%, 30-80%, or >80%). Results were compared to the Funaki classification using receiver-operating-characteristic (ROC) curve analysis, with statistical significance being tested with the Chi-square test. RESULTS: A statistically significant negative correlation (Spearman's ρ = -0.31, p-value < 0.05) was detected between ADC values and NPV ratios. ROC curve analysis indicated that optimal ADC cutoff values of 980 × 10-6mm2/s (NPVr > 80%) and 1800 × 10-6mm2/s (NPVr < 30%) made it possible to classify fibroids into three groups: ADC I (NPVr > 80%), ADC II (NPVr 30-80%) and ADC III (NPVr < 30%). Analysis of the whole model area under the curve resulted in values of 0.79 for the ADC classification (p-value = 0.0007) and 0.62 for the Funaki classification (p-value = 0.0527). CONCLUSIONS: Lower ADC values prior to treatment correlate with higher NPV ratios. The ADC classification seems to be able to predict the NPV ratio and may even outperform the Funaki classification. Based on these results DWI and ADC maps should be included in the MRI screening protocol.

Transcriptomic responses to hypoxia in endometrial and decidual stromal cells.

Human reproductive success depends on a properly decidualized uterine endometrium that allows implantation and the formation of the placenta. At the core of the decidualization process are endometrial stromal fibroblasts (ESF) that differentiate to decidual stromal cells (DSC). As variations in oxygen levels are functionally relevant in endometrium both upon menstruation and during placentation, we assessed the transcriptomic responses to hypoxia in ESF and DSC. In both cell types, hypoxia-upregulated genes in classical hypoxia pathways such as glycolysis and the epithelial mesenchymal transition. In DSC, hypoxia restored an ESF-like transcriptional state for a subset of transcription factors that are known targets of the progesterone receptor, suggesting that hypoxia partially interferes with progesterone signaling. In both cell types, hypoxia modified transcription of several inflammatory transcription factors that are known regulators of decidualization, including decreased transcription of STATs and increased transcription of CEBPs. We observed that hypoxia-upregulated genes in ESF and DSC had a significant overlap with genes previously detected to be upregulated in endometriotic stromal cells. Promoter analysis of the genes in this overlap suggested the hypoxia-upregulated Jun/Fos and CEBP transcription factors as potential drivers of endometriosis-associated transcription. Using immunohistochemistry, we observed increased expression of JUND and CEBPD in endometriosis lesions compared to healthy endometria. Overall, the findings suggest that hypoxic stress establishes distinct transcriptional states in ESF and DSC and that hypoxia influences the expression of genes that contribute to the core gene regulation of endometriotic stromal cells.

Oxytocin selectively reduces blood flow in uterine fibroids without an effect on myometrial blood flow: a dynamic contrast enhanced MRI evaluation.

INTRODUCTION: Uterine fibroids are the most common benign neoplasms in women. The administration of intravenous oxytocin is known to increase the efficacy of a non-invasive thermal ablation method (MR-HIFU) for treating fibroids. However, it is not known whether this phenomenon is caused by the effect of the oxytocin on the myometrium or the fibroid itself. The objective of this study was to evaluate the influence of oxytocin on the blood flow of fibroids, myometrium and skeletal muscle using a quantitative perfusion MRI technique. MATERIALS AND METHODS: 17 premenopausal women with fibroids considered to be treated with MR-HIFU and 11 women with no fibroids were enrolled in the study. An extended MRI protocol of the pelvis was acquired for each subject. Later another MRI scan was performed with continuous intravenous infusion of oxytocin. The effect of oxytocin was analyzed from quantitative perfusion imaging. The study was registered in clinicaltrials.gov NCT03937401. RESULTS: Oxytocin decreased the blood flow of each fibroid; the median blood flow of fibroid was 39.9 ml/100 g tissue/min without and 3.5 mL/100 g/min with oxytocin (p ≤ 0.0001). Oxytocin did not affect the blood flow of the myometrium in either group. Oxytocin increased the blood flow of the skeletal muscle in both groups (p = 0.04). CONCLUSION: Oxytocin is effective in decreasing the blood flow in fibroids while having minor or no effect on the blood flow of normal myometrium. Routine use of oxytocin in HIFU therapy may make the therapy suitable to a larger group of women in a safe manner.

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.

Microdissection testicular sperm extraction in Finland - results of the first 100 patients.

INTRODUCTION: Testicular microdissection sperm extraction (MD-TESE) combined with intracytoplasmic sperm injection (ICSI) has made biological fatherhood possible for many men with the most severe form of male infertility, non-obstructive azoospermia. MD-TESE was introduced in Turku in 2008, and by 2015, 100 Finnish men with non-obstructive azoospermia have been operated on. MATERIAL AND METHODS: The average age of the men was 33 years at the time of surgery. Forty-eight had a needle biopsy previously and 56% had a testicular size <15 mL. The most common diagnoses were idiopathic (n = 65), Klinefelter syndrome (n = 15), operated cryptorchidism or torsion (n = 10), and Y chromosome microdeletion (n = 7). The pregnancy outcomes were followed. RESULTS: The sperm recovery rate (SRR) overall was 42%: 31% for idiopathic non-obstructive azoospermia, 40% for Klinefelter syndrome, 57% for Y chromosome microdeletion AZFc, 90% for previous testicular surgery (mostly for cryptorchidism; n = 10) and 67% for previous cytotoxic treatment (n = 3). SRR with histopathologic diagnosis Sertoli-cell-only was 29%, and 44% for spermatogenic arrest. Age did not affect the outcome of the surgery. Small testicular size seemed to predict a higher SRR. A previous needle biopsy did not predict a lower SRR. Surgical complications were rare. Of couples, 32 had at least one ICSI attempt, and 22 at least one live birth, giving a cumulative live birth rate of 69%. No major pregnancy complications occurred. CONCLUSIONS: Our SRR is comparable with international results, and the cumulative live birth rate similar to other ICSI indications in Finland. Physicians and specialists need to be made aware of new treatment options to enable biological fatherhood for men with non-obstructive azoospermia.

Roles of human epididymis protein 4, carbohydrate antigen 125, inhibin B and anti-Müllerian hormone in the differential diagnosis and follow-up of ovarian granulosa cell tumors.

OBJECTIVE: Evaluation of circulating tumor markers in ovarian cancer is crucial for optimal patient care. The goal of this study was to verify the most accurate circulating tumor markers for the diagnosis and follow-up of adult-type granulosa cell tumors (AGCTs). METHODS: The levels of circulating human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125), together with AGCT markers inhibin B and anti-Müllerian hormone (AMH), were measured in 135 samples from AGCT patients, 37 epithelial ovarian carcinoma (EOC) patients, and 40 endometrioma (ENDO) patients. The levels were plotted with receiver operating characteristic (ROC) graphs, and the area under the curves (AUC) of the different markers were calculated and compared. RESULTS: HE4 levels were significantly lower in AGCTs than in EOCs (p<0.0001). CA125 levels were above 35IU/l in 25% of AGCT patients and 47.5% of ENDO patients, whereas inhibin B and AMH levels were elevated only in patients with AGCTs. In the AUC comparison analyses, inhibin B alone was sufficient to differentiate AGCT from EOC. In differentiating AGCT from ENDO, inhibin B and AMH performed similarly, and the combination of inhibin B and AMH increased the accuracy compared to either marker alone (sensitivity, 100%; specificity, 93%). Among AGCT patients, inhibin B was the best marker for detecting the presence of AGCT. CONCLUSIONS: HE4 and CA125 levels were low in AGCTs, and inhibin B was the most accurate circulating biomarker in distinguishing AGCTs from EOCs and from ENDOs. Inhibin B was also the best single marker for AGCT follow-up.

A Nanoparticle-Lectin Immunoassay Improves Discrimination of Serum CA125 from Malignant and Benign Sources.

BACKGROUND: Measurement of serum cancer antigen 125 (CA125) is the standard approach for epithelial ovarian cancer (EOC) diagnostics and follow-up. However, the clinical specificity is not optimal because increased values are also detected in healthy controls and in benign diseases. CA125 is known to be differentially glycosylated in EOC, potentially offering a way to construct CA125 assays with improved cancer specificity. Our goal was to identify carbohydrate-reactive lectins for discriminating between CA125 originating from EOC and noncancerous sources. METHODS: CA125 from the OVCAR-3 cancer cell line, placental homogenate, and ascites fluid from patients with cirrhosis were captured on anti-CA125 antibody immobilized on microtitration wells. A panel of lectins, each coated onto fluorescent europium-chelate-doped 97-nm nanoparticles (Eu(+3)-NPs), was tested for detection of the immobilized CA125. Serum samples from high-grade serous EOC or patients with endometriosis and healthy controls were analyzed. RESULTS: By using macrophage galactose-type lectin (MGL)-coated Eu(+3)-NPs, an analytically sensitive CA125 assay (CA125(MGL)) was achieved that specifically recognized the CA125 isoform produced by EOC, whereas the recognition of CA125 from nonmalignant conditions was reduced. Serum CA125(MGL) measurement better discriminated patients with EOC from endometriosis compared to conventional immunoassay. The discrimination was particularly improved for marginally increased CA125 values and for earlier detection of EOC progression. CONCLUSIONS: The new CA125(MGL) assay concept could help reduce the false-positive rates of conventional CA125 immunoassays. The improved analytical specificity of this test approach is dependent on a discriminating lectin immobilized in large numbers on Eu(+3)-NPs, providing both an avidity effect and signal amplification.

Semen quality improves marginally during young adulthood: a longitudinal follow-up study.

STUDY QUESTION: Does semen quality improve during early adulthood? SUMMARY ANSWER: Semen variables change little during the third decade of life, however some improvement in sperm morphology and motility may occur. WHAT IS KNOWN ALREADY: A suspicion of deteriorating semen quality has been raised in several studies. The longitudinal development of semen quality in early adulthood is insufficiently understood. STUDY DESIGN, SIZE, DURATION: A longitudinal follow-up of two cohorts of volunteer young adult Finnish men representing the general population was carried out. Cohorts A (discovery cohort, born 1979-1981, n = 336) and B (validation cohort, born 1983, n = 197) were followed up from the age of 19 years onward for 10 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria included that both the men and their mothers were born in Finland. Semen analysis was performed in cohorts A and B at 2-4 year intervals over a period of 10 years. Semen volume, sperm concentration, total sperm count, motility, total motile count and morphology were the variables assessed in the analysis. A physical examination was carried out at each visit to detect any significant andrological abnormalities. The overall participation rate was 13.4%. MAIN RESULTS AND THE ROLE OF CHANCE: During the follow-up, the percentage of sperm with normal morphology and the percentage of motile sperm increased significantly both in the discovery (A) (P < 0.001 at 19 versus 29 years for both) and validation (B) (P < 0.001 and P = 0.03 at 19 versus 29 years, respectively) cohort. Sperm concentration and total sperm count showed a significant increase with age only in cohort B (P = 0.03 at 21 versus 29 years, P = 0.009 at 19 versus 29 years, respectively). LIMITATIONS, REASONS FOR CAUTION: A limited number of men participated both in the first round and in the final fourth round (cohort A, n = 111 and cohort B, n = 90 men) and in all four rounds (cohort A, n = 61 and cohort B, n = 52). WIDER IMPLICATIONS OF THE FINDINGS: Almost full spermatogenic capacity is reached by the age of 19 years. However, the improvement in sperm motility and morphology during early adulthood may slightly improve male fecundity. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the European Commission (QLK4-CT-1999-01422, QLK4-CT-2001-00269, QLK4-2002-0063, FP7/2008-2012: DEER 212844), The Danish Medical Research Council (9700833, 9700909), Danish Agency for Science (Technology and Innovation 09-067180), the Svend Andersen's Foundation, Velux Foundation, and Novo Nordisk Foundation, the Turku University Hospital, Sigrid Jusélius Foundation and the Academy of Finland. There are no conflicts of interest.

[Supraventricular tachycardia during pregnancy]. / Raskaudenaikainen supraventrikulaarinen takykardia.

An increase in cardiac output during pregnancy increases the risk of arrhythmias for the expectant mother. Supraventricular tachycardia (SVT) underlies the sensations of arrhythmia in a pregnant woman in as many as one sixth of the cases. Vagal nerve (n. vagus) stimulation and adenosine serve as first-line treatment, but electrical cardioversion is likely to be a safe alternative as well. We describe a case in which the SVT of a woman in the third trimester of pregnancy was unresponsive to vagal nerve stimulation and pharmacological treatments. Electrical cardioversion was successfully performed after having a cesarean section procedure.

[How to interpret a semen sample?]. / Miten tulkitsen spermanäytteen?

Semen sample belongs to the basic examinations for couples suffering from infertility. To ascertain reliable results, the patients must be provided with adequately detailed instructions regarding the sample collection. The interpretation should not aim at a too precise appraisal about fertility. On the other hand, causes for the semen's clearly impaired ability to fertilize must be solved without delay. Good anamnesis will help to interpret the semen analysis and accelerate and direct further exploration. The semen sample should always be repeated, if the answer clearly deviates from normal.

Ovarian endometriosis signatures established through discovery and directed mass spectrometry analysis.

New molecular information on potential therapeutic targets or tools for noninvasive diagnosis for endometriosis are important for patient care and treatment. However, surprisingly few efforts have described endometriosis at the protein level. In this work we enumerate the proteins in patient endometrium and ovarian endometrioma by extensive and comprehensive analysis of minute amounts of cryosectioned tissues in a three-tiered mass spectrometric approach. Quantitative comparison of the tissues revealed 214 differentially expressed proteins in ovarian endometrioma and endometrium. These proteins are reported here as a resource of SRM (selected reaction monitoring) assays that are unique, standardized, and openly available. Pathway analysis of the proteome measurements revealed a potential role for Transforming growth factor ß-1 in ovarian endometriosis development. Subsequent mRNA microarray analysis further revealed clear ovarian endometrioma specificity for a subset of these proteins, which was also supported by further in silico studies. In this process two important proteins emerged, Calponin-1 and EMILIN-1, that were additionally confirmed in ovarian endometrioma tissues by immunohistochemistry and Western blotting. This study provides the most comprehensive molecular description of ovarian endometriosis to date and researchers with new molecular methods and tools for high throughput patient screening using the SRM assays.

Serum concentrations of HE4 change little during in vitro fertilization.

OBJECTIVE: Human epididymal secretory protein 4 (HE4) is a biomarker for ovarian cancer. The effect of follicle stimulating hormone (FSH) stimulation during in vitro fertilization (IVF) on HE4 was evaluated to determine whether substantial hormonal stimulation of the ovaries affects the serum levels of this marker. Findings were compared with serum concentrations of cancer antigen 125 (CA125), currently the most commonly used marker for ovarian cancer. DESIGN: Prospective cohort study. SETTING: University hospital infertility clinic. POPULATION: Infertility patients undergoing IVF treatment. METHODS: We determined the serum concentration of HE4 and CA125 in serial blood samples in 20 women treated with IVF. Samples were taken following gonadotrophin-releasing hormone agonist suppression, two to three times during FSH stimulation, at ovum pick-up and 2 weeks following embryo transfer at the time of the pregnancy test. Ovarian follicles were counted and serum estradiol concentrations measured throughout treatment. MAIN OUTCOME MEASURES: Serum HE4, CA125 and estradiol concentrations. RESULTS: Serum HE4 levels did not increase significantly during the FSH stimulation. The majority of values remained below the normal reference range (<70 pm) throughout the treatment. Serum CA125 concentration also remained low during stimulation. Serum estradiol concentration reflected the severity of ovarian stimulation during IVF, increasing 3.9-fold with stimulation. CONCLUSIONS: Serum HE4 concentrations respond little if at all to supraphysiological ovarian stimulation, suggesting that the amount of circulating HE4 in women with normal ovaries is independent of gonadotropin stimulation. Hormonal stimulation of the ovaries is unlikely to affect the differential diagnosis of ovarian tumors with HE4.

ICSI outcome after microdissection testicular sperm extraction, testicular sperm aspiration and ejaculated sperm.

We conducted a case-controlled single-center cohort study to evaluate the intracytoplasmic sperm injection (ICSI) outcome in severe male infertility with different methods of sperm obtention. The data was compiled from a tertiary university hospital. The micro-TESE procedures were performed from 2008 to 2023, with a sperm recovery rate (SRR) of 45 %. The ICSI treatments were carried out between 2011 and 2023. The aim of the study was to compare the ICSI outcome using sperm obtained by microdissection testicular extraction (micro-TESE), testicular sperm aspiration (TESA), and ejaculated sperm with sperm concentration less than 15 million per milliliter. We included a total of 462 ICSI cycles, of which 340 ICSIs with ejaculated sperm of men with oligozoospermia, with or without asthenozoospermia or teratozoospermia (OAT group), 51 ICSIs with TESA sperm of men with obstructive azoospermia (OA, TESA group), and 71 ICSIs with micro-TESE sperm of men with non-obstructive azoospermia (NOA, micro-TESE group). The patient characteristics, fertilization rate, pregnancy rate, and pregnancy outcome data were similar between the groups. The fertilization rates were 66.0 % in the OAT group, 68.3 % in the TESA group and 62.8 % in the micro-TESE group and live birth rate per embryo transfer were 23.7 %, 28.9 %, and 25.0 %, respectively, without statistical difference. The obstetrical outcome was similar in all the groups. The overall clinical results in all ICSI cycles performed for treating severe male factor infertility were similar, independent of the method of collection of spermatozoa. The results also confirm the efficacy of micro-TESE in the treatment of severe male factor infertility.