Complete or partial loss of the Y chromosome in an unselected cohort of 865 non-vasectomized, azoospermic men.

BACKGROUND: Structural abnormalities as well as minor variations of the Y chromosome may cause disorders of sex differentiation or, more frequently, azoospermia. This study aimed to determine the prevalence of loss of Y chromosome material within the spectrum ranging from small microdeletions in the azoospermia factor region (AZF) to complete loss of the Y chromosome in azoospermic men. RESULTS: Eleven of 865 azoospermic men (1.3%) collected from 1997 to 2022 were found to have a karyotype including a 45,X cell line. Two had a pure 45,X karyotype and nine had a 45,X/46,XY mosaic karyotype. The AZF region, or part of it, was deleted in eight of the nine men with a structural abnormal Y-chromosome. Seven men had a karyotype with a structural abnormal Y chromosome in a non-mosaic form. In addition, Y chromosome microdeletions were found in 34 men with a structural normal Y chromosome. No congenital malformations were detected by echocardiography and ultrasonography of the kidneys of the 11 men with a 45,X mosaic or non-mosaic cell line. CONCLUSIONS: In men with azoospermia, Y chromosome loss ranging from small microdeletions to complete loss of the Y chromosome was found in 6.1% (53/865). Partial AZFb microdeletions may give a milder testicular phenotype compared to complete AZFb microdeletions.

RéSUMé: CONTEXTE: Des anomalies structurelles ainsi que des variations mineures du chromosome Y peuvent provoquer des troubles de la différenciation sexuelle ou, plus fréquemment, une azoospermie. Cette étude visait à déterminer la prévalence de la perte de matériel chromosomique Y dans le spectre allant de petites microdélétions dans la région du facteur d'azoospermie (AZF) à la perte complète du chromosome Y chez les hommes azoospermiques. RéSULTATS: Onze des 865 hommes azoospermiques (1,3 %), collectés entre 1997 et 2022, présentaient un caryotype comprenant une lignée cellulaire 45,X. Deux avaient un caryotype pur 45,X et neuf avaient un caryotype mosaïque 45,X/46,XY. La région AZF, ou une partie de celle-ci, était absente chez huit des neuf hommes présentant un chromosome Y anormal sur le plan structurel. Sept hommes présentaient un caryotype avec un chromosome Y structurellement anormal sous une forme non mosaïque. De plus, des microdélétions du chromosome Y ont été trouvées chez 34 hommes présentant un chromosome Y de structure normale. Aucune malformation congénitale n'a été détectée par échocardiographie et échographie des reins des 11 hommes porteurs d'une lignée cellulaire 45,X mosaïque ou non mosaïque. CONCLUSIONS: Chez les hommes qui ont une azoospermie, une perte du chromosome Y, allant de petites microdélétions à une perte complète du chromosome Y, a été observée chez 6,1 % (53/865). Les microdélétions partielles de la région AZFb peuvent donner un phénotype testiculaire plus doux que les microdélétions complètes de l'AZFb.

Reduction of serum-induced endothelial STAT3(Y705) activation is associated with preeclampsia.

OBJECTIVES: Preeclampsia is associated with maternal morbidity and mortality during pregnancy, and also an increased cardiovascular disease (CVD) risk later in life. During preeclampsia, alterations in secreted placental factors leading to systemic maternal endothelial dysfunction are evident. However, little is known about the associated endothelial intracellular signaling. STAT3 is a latent cytoplasmic transcription factor involved in endothelial cell differentiation, survival, and angiogenesis. We aimed to test if preeclampsia and preeclampsia-related placental factors could alter serum-induced STAT3(Y705) activation in endothelial cells. Furthermore, if altered serum-induced endothelial STAT3 (Y705) activation is related to post-preeclamptic CVD risk. STUDY DESIGN: HUVECs were used as a model of maternal endothelium. Experiments entailed addition of 20% human pregnancy serum as well as addition of recombinant PlGF, sFLT1 and VEGF-A165a to the cells. MAIN OUTCOME MEASURES: Levels of pSTAT3(Y705) related to STAT3 levels were evaluated by immunoblotting analysis. RESULTS: Our results show that preeclamptic serum induces significantly lower STAT3(Y705) phosphorylation compared with uncomplicated pregnancy serum (P = 0.0089) in endothelial cells. Furthermore, STAT3(Y705) phosphorylation was not changed upon addition of PlGF, sFLT1, or VEGF-A165a together with pregnancy sera compared with sera alone. Finally, sera from women with previous preeclampsia and current hypertension and carotid atherosclerotic plaques show significantly lower STAT3(Y705) phosphorylation capabilities compared with healthy women with previous uncomplicated pregnancies 8-18 years after deliveries (P = 0.029). CONCLUSIONS: Reduction in serum-induced endothelial STAT3(Y705) activation may play an important role in the preeclampsia-associated endothelial dysfunction. Additionally, reduced endothelial STAT3(Y705) phosphorylation may contribute to increased post-preeclamptic CVD risk 8-18 years after delivery.

Developmental stage and morphology of the competent blastocyst are associated with sex of the child but not with other obstetric outcomes: a multicenter cohort study.

STUDY QUESTION: Are transfer day, developmental stage and morphology of the competent blastocyst in pregnancies leading to live birth associated with preterm birth, birthweight, length at birth and sex of the child? SUMMARY ANSWER: A high score in blastocyst developmental stage and in trophectoderm (TE) showed a significant association with the sex of the child, while no other associations with obstetric outcomes were observed. WHAT IS KNOWN ALREADY: The association between blastocyst assessment scores and obstetric outcomes have been reported in small single-center studies and the results are conflicting. STUDY DESIGN, SIZE, DURATION: Multicenter historical cohort study based on exposure data (transfer day (blastocyst developmental stage reached by Day 5 or Day 6)) blastocyst developmental stage (1-6) and morphology (TE and inner cell mass (ICM): A, B, C)) and outcome data (preterm birth, birthweight, length at birth, and sex of the child) from women undergoing single blastocyst transfer resulting in a singleton pregnancy and live birth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 16 private and university-based facilities for clinical services and research were used. A total of 7246 women, who in 2014-2018 underwent fresh-embryo transfer with a single blastocyst or frozen-thawed embryo transfer (FET) with a single blastocyst resulting in a singleton pregnancy were identified. Linking to the Danish Medical Birth Registry resulted in a total of 4842 women with a live birth being included. Cycles with pre-implantation genetic testing and donated gametes were excluded. The analyses were adjusted for female age (n = 4842), female BMI (n = 4302), female smoking (n = 4290), parity (n = 4365), infertility diagnosis (n = 4765), type of treatment (n = 4842) and center (n = 4842); some analyses additionally included gestational age (n = 4368) and sex of the child (n = 4833). MAIN RESULTS AND THE ROLE OF CHANCE: No statistically significant associations between blastocyst assessment scores (transfer day, developmental stage, TE, ICM) and preterm birth (8.3%) or birthweight (mean 3461.7 g) were found. The adjusted association between blastocysts with a TE score of C and a TE score of A and length at birth (mean 51.6 cm) were statistically significant (adjusted mean difference 0.4 cm (95% CI: 0.02; 0.77)). Blastocysts transferred with developmental stage score 5 compared to blastocysts transferred with score 3 had a 34% increased probability of being a boy (odds ratio (OR) 1.34 (95% CI: 1.09; 1.64). Further, TE score B blastocysts compared to TE score A blastocysts had a 31% reduced probability of being a boy (OR 0.69 (95% CI: 0.60; 0.80)). LIMITATIONS, REASONS FOR CAUTION: It is possible that some residual confounding remains. WIDER IMPLICATIONS OF THE FINDINGS: Blastocyst selection during ART does not appear to introduce any negative effects on obstetric outcome. Therefore, clinicians and patients can be reassured that the assessment scores of the selected blastocyst will not in themselves pose a risk of preterm birth or affect birthweight and the length at birth. STUDY FUNDING/COMPETING INTEREST(S): Unrestricted grant from Gedeon Richter Nordics AB, Sweden. None of the authors have any competing interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Reduced coronary flow velocity reserve in women with previous pre-eclampsia: link to increased cardiovascular disease risk.

OBJECTIVES: To evaluate differences in coronary microvascular function approximately 12 years after delivery between women who had had early- (EO-PE) or late- (LO-PE) onset pre-eclampsia and those who had had a normotensive pregnancy, and to assess the relationship between microvascular function and myocardial deformation at follow-up in these women. METHODS: This was a case-control study of 88 women who had delivered at the Department of Gynecology and Obstetrics, Randers Regional Hospital, Randers, Denmark, between 1998 and 2008. Coronary flow velocity reserve (CFVR) was assessed by Doppler echocardiography approximately 12 years after delivery. Women were grouped according to whether the pregnancy had been complicated by EO-PE (n = 29) or LO-PE (n = 20), or had been normotensive (controls) (n = 39). Study groups were matched for maternal age and time since delivery. CFVR at follow-up was compared between the study groups. Regression analysis was used to assess the association between gestational age at onset of PE and CFVR. The association between left ventricular global longitudinal strain (LV-GLS) and CFVR at follow-up was also evaluated. RESULTS: Resting coronary flow velocity assessed 12 years after delivery was comparable between the study groups (P = 0.55), whereas peak hyperemic flow velocity was significantly lower in the EO-PE group than in the LO-PE group (P < 0.01) and controls (P < 0.0001). As such, mean CFVR at follow-up was significantly lower in the EO-PE group than in the LO-PE group (P < 0.01) and controls (P < 0.0001). CFVR was < 2.5 in 48% of women in the EO-PE group, 25% of those in the LO-PE group and 8% of controls (P < 0.01). There was a significant positive association between gestational age at diagnosis of PE and CFVR at 12-year follow-up (ß1 = 1.8 (95% CI, 0.8-2.9); P < 0.01). This relationship remained significant after adjustment for cardiovascular risk factors, namely mean arterial blood pressure, glycated hemoglobin level, body mass index, low-density lipoprotein cholesterol level and smoking status (P < 0.05). There was a significant association between LV-GLS and CFVR in women who had had PE (ß1 = -1.5 (95% CI, -2.2 to -0.9); R2 = 0.33, P < 0.0001). CONCLUSIONS: Low gestational age at onset of PE, both as a continuous variable and when categorized as early onset, was associated with decreased CFVR 12 years after delivery. Nearly 50% of women who had had EO-PE had CFVR < 2.5 at follow-up. Reduced CFVR in women who had had PE was associated with subclinical myocardial dysfunction in terms of reduced LV-GLS. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

The influence of omega-3 fatty acids on semen quality markers: a systematic PRISMA review.

BACKGROUND: Infertility affects about 15% of all couples worldwide. Male factors such as decreased semen quality contribute to around 40% of the cases. Recent reviews have shown that different foods and nutrients may improve semen quality. OBJECTIVES: We conducted a systematic review in order to investigate whether intake of omega-3 fatty acids can improve semen quality markers. MATERIALS AND METHODS: A systematic search of PubMed, Embase, and Cochrane was conducted in adherence with the PRISMA guideline from the earliest available online indexing year to October 2018. Keywords related to male fertility or infertility was combined with words describing omega-3 fatty acids and dietary fish intake. RCTs and observational studies on infertile and fertile men were included. Studies were considered eligible if they met the inclusion criteria, evaluated either the effect of omega-3 fatty acids or dietary fish intake and had semen quality as primary outcome. RESULTS: Thousand and seventy four records were screened, and sixteen studies were ultimately included. Fourteen of the included studies found an improvement or association between omega-3 and at least one semen quality marker. As the studies were very inhomogeneous in participants (fertile/infertile, age, BMI, ethnicity etc), no meta-analysis was performed. DISCUSSION: The findings in this review are limited by the few available RCTs. Furthermore, RCTs were very heterogenetic according to study population, sample size, dosage of omega-3, and durations of follow up. Results from the observational studies might have been affected by recall bias and confounded by lifestyle factors. CONCLUSION: Based on the findings in this review, omega-3 supplements and dietary intake of omega-3 might improve semen quality parameters in infertile men and men from couples seeking fertility treatment. However, more research is required in order to fully clarify the effect of omega-3 on semen quality and research with fecundity as end point is needed.

Low risk of venous thromboembolism following early pregnancy loss in pregnancies conceived by IVF.

STUDY QUESTION: What is the risk of venous thromboembolism (VTE) in the 12 weeks following early pregnancy loss in pregnancies conceived by IVF? SUMMARY ANSWER: The VTE risk is low in the 12 weeks following early pregnancy loss in pregnancies conceived by IVF. WHAT IS KNOWN ALREADY: There is an excess VTE risk during first trimester in complete IVF pregnancies leading to delivery. It is unknown whether this excess VTE risk also is present in IVF pregnancies terminated by early pregnancy loss (implantation failure, missed abortion, or spontaneous or induced abortion before 10 completed gestational weeks). STUDY DESIGN, SIZE, DURATION: A nationwide registry-based cohort study including all Danish IVF pregnancies registered in the Danish IVF Register between 1995 and 2005. Women who underwent frozen embryo replacement or oocyte donation were not included. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included all 24 931 IVF treatments leading to pregnancy among 19 260 women. We identified 16 701 complete IVF pregnancies, 7567 IVF pregnancies with early pregnancy loss, and 663 IVF pregnancies terminated by late abortion (≥gestational weeks 10). We followed women for 12 weeks after termination of pregnancy and calculated the absolute risk of VTE during follow-up with 95% CI. As a relative risk estimate, we calculated the risk ratio for VTE following IVF pregnancies with early loss compared to the VTE risk following complete IVF pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE: During the 12 weeks of follow-up, only one case of VTE occurred in the group of early pregnancy loss, none in the late abortion group, and 13 VTE cases occurred in complete IVF pregnancies. The VTE risk per 10 000 pregnancies was 1.3 [0.03-7.4] for IVF pregnancies with early loss and 7.8 [4.1-13.3] for complete pregnancies; the corresponding risk ratio was 0.17 [0.02-1.3]. Thus, we found a low absolute VTE risk in the 12 weeks following early pregnancy loss in IVF pregnancies. The relative VTE risk was low in comparison to the VTE risk in early gestation reported for complete IVF pregnancies and for Danish background pregnancies. LIMITATIONS, REASONS FOR CAUTION: Despite the use of complete nationwide data, only a few VTE events were available for the statistical analyses thereby limiting the precision of our estimates. We included both inpatient and outpatient VTE hospital diagnoses, but we cannot rule out the occurrence of VTE cases not diagnosed at hospital and hence not registered in the National Patient Registry. No information was available on the use of prophylactic low molecular weight heparin: access to such might have helped to explain our findings, but would not have changed our conclusions. WIDER IMPLICATIONS OF THE FINDINGS: The results of the present study do not indicate a need for prophylactic anticoagulant therapy in women suffering early IVF pregnancy loss without other risk factors. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. There are no conflicts of interest to declare.

Timing of human preimplantation embryonic development is confounded by embryo origin.

STUDY QUESTION: To what extent do patient- and treatment-related factors explain the variation in morphokinetic parameters proposed as embryo viability markers? SUMMARY ANSWER: Up to 31% of the observed variation in timing of embryo development can be explained by embryo origin, but no single factor elicits a systematic influence. WHAT IS KNOWN ALREADY: Several studies report that culture conditions, patient characteristics and treatment influence timing of embryo development, which have promoted the perception that each clinic must develop individual models. Most of the studies have, however, treated embryos from one patient as independent observations, and only very few studies that evaluate the influence from patient- and treatment-related factors on timing of development or time-lapse parameters as predictors of viability have controlled for confounding, which implies a high risk of overestimating the statistical significance of potential correlations. STUDY DESIGN, SIZE, DURATION: Infertile patients were prospectively recruited to a cohort study at a hospital fertility clinic from February 2011 to May 2013. Patients aged <38 years without endometriosis were eligible if ≥8 oocytes were retrieved. Patients were included only once. All embryos were monitored for 6 days in a time-lapse incubator. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1507 embryos from 243 patients were included. The influence of fertilization method, BMI, maternal age, FSH dose and number of previous cycles on timing of t2-t5, duration of the 2- and 3-cell stage, and development of a blastocoel (tEB) and full blastocoel (tFB) was tested in multivariate, multilevel linear regression analysis. Predictive parameters for live birth were tested in a logistic regression analysis for 223 single transferred blastocysts, where time-lapse parameters were investigated along with patient and embryo characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Moderate intra-class correlation coefficients (0.16-0.31) were observed for all parameters except duration of the 3-cell stage, which demonstrates that embryos from one patient elicit clustering at a patient level. No single patient- and treatment-related factor was found to systematically influence the timing from cleavage to blastocyst stage, which indicates that no individual patient-related factor can be identified that separately explains the clustering throughout the entire developmental stages. The blastocyst parameters were more affected by patient-related factors than cleavage stage parameters, as tEB occurred significantly later with older age (0.29 h/year (95% confidence interval: CI 0.03; 0.56)), while both tEB and tFB occurred significantly later with increasing dose of FSH (tEB: 0.12 h/100 IU FSH (95% CI 0.01;0.24); tFB 0.14 h/100 IU FSH (95% CI 0.03;0.27)) and with more previous attempts (tEB: 1.2 h/attempt (95% CI 0.01;2.5); tFB 1.4 h/attempt (0.10;2.7)). Fertilization method affected timing of the first division, with ICSI embryos cleaving significantly faster than IVF embryos (-3.6% (95% CI -6.4; -0.77)), whereas no difference was found in the subsequent divisions. The univariable regression analysis identified female age, cumulative FSH dose, degree of blastocyst expansion, score of the inner cell mass and timing of full blastocyst formation as predictors of live birth. The timing of full blastocyst formation (tFB) did not remain significant when adjusting for age, number of previous cycles and cumulative FSH dose, which were the parameters shown to influence tFB in the mixed regression model. LIMITATIONS, REASONS FOR CAUTION: Only good prognosis patients were enrolled, so these results may not be generalized to all infertile women. Not all patient-related factors were investigated. WIDER IMPLICATIONS OF THE FINDINGS: Our findings underline the importance of treating embryos as dependent observations and suggest a high risk of patient-based confounding in retrospective studies. The impact of confounders and the embryo origin needs to be addressed in order to apply appropriate statistical models in observational studies. Furthermore, this observation emphasizes the need for RCTs for evaluating use of time-lapse parameters for embryo selection. STUDY FUNDING/COMPETING INTERESTS: Funding for the cohort study was provided by the Lippert Foundation, the Toyota Foundation, the Aase og Einar Danielsen foundation and NordicInfu Care research grant. Research at the Fertility Clinic, Aarhus University Hospital is supported by an unrestricted grant from MSD and Ferring. K.K. is funded by a grant from the Danish Council for Independent Research Medical Sciences. The authors declare no competing interest.

A robust immunoassay for pregnancy-associated plasma protein-A2 based on analysis of circulating antigen: establishment of normal ranges in pregnancy.

Pregnancy-associated plasma protein-A (PAPP-A) and PAPP-A2, two homologous metzincin metalloproteases, are both tightly linked to regulation within the insulin-like growth factor (IGF) system because of their specific cleavage of IGF binding proteins. Recent studies suggest that PAPP-A may be involved in clinical conditions related to unwanted cellular growth, and the circulating levels of PAPP-A is an established biomarker in prenatal screening for chromosomal abnormalities. Microarray data indicate that PAPP-A2 has potential as a biomarker for pre-eclampsia. However, well-characterized immunological methods of quantification are not available. We therefore developed monoclonal antibodies against recombinant PAPP-A2. The antibodies were epitope mapped against recombinantly expressed chimeras between PAPP-A2 and PAPP-A. Furthermore, circulating PAPP-A2 was immunoaffinity purified and characterized by sequence analysis and mass spectrometry. Unlike PAPP-A, PAPP-A2 is a noncovalent dimer in which each subunit of 1558 amino acids originates from all of the 22 predicted coding exons. A previously hypothesized variant (PAPP-E) does not exist, but low amounts of a C-terminally truncated PAPP-A2 variant was detected. A sensitive and robust ELISA for full-length PAPP-A2 was developed and used to establish normal ranges of PAPP-A2 through pregnancy. The functional sensitivity of this ELISA at 20% CV was 0.08 ng/ml, and the serum concentration of PAPP-A2 was found to increase during pregnancy in agreement with placental synthesis. The existence of this assay will enable an assessment of the biomarker potential of PAPP-A2 in pre-eclampsia as well as other clinical conditions.

Endometriosis, dysmenorrhoea and diet.

OBJECTIVE: To review the literature on the effects of diet on endometriosis and dysmenorrhoea. STUDY DESIGN: A systematic search for trials investigating a relationship between diet and endometriosis/dysmenorrhoea was undertaken, and 23 studies were included in this review. RESULTS: Data on the relationship between diet and endometriosis were limited to 12 trials, three of which were animal studies, resulting in a total of 74,708 women. One large study (n=70,709) found a relatively strong association between endometriosis and trans-fatty acid consumption, and a lower risk of endometriosis with increased consumption of long-chain omega-3 fatty acids. The latter finding was also supported by smaller studies. No further dietary recommendations for reducing the risk of endometriosis were possible, and results for intake of vegetable, fibre and fruit were equivocal. The relationship between diet and dysmenorrhoea was investigated in 11 trials with different designs, including a total of 1433 women. Intake of fish oil seemed to reduce dysmenorrhoea. CONCLUSION: The literature on endometriosis and dysmenorrhoea in relation to diet is sparse, yielding equivocal results on specific elements. Overall, however, the literature suggests that specific types of dietary fats are associated with endometriosis and/or dysmenorrhoea, thereby indicating that there may be modifiable risk factors. Further research is recommended on both subjects.

First trimester abortion with mifepristone and vaginal misoprostol.

This study assessed the efficacy and side effects of first trimester medical abortion using mifepristone and vaginally administered misoprostol. Medical abortion was first introduced in Denmark in December 1997, and the acceptability of this new approach in a Danish population was evaluated. The study included the first 100 women seeking medical abortion. The gestational age was from 33 to 56 days. All received 600 mg mifepristone (RU 486) orally followed 2 days later by vaginally administered misoprostol 400 microg. Success was defined as achieving complete abortion without the need for surgical evacuation. Ninety-three percent achieved a successful medical termination of pregnancy. Side effects were few, and the acceptability was high. Ninety percent of the women would prefer medical abortion in case of a new unwanted pregnancy. The combination of mifepristone and vaginally administrated misoprostol is effective, safe, has few side effects and is well accepted by Danish women.

Telomerase activity, MIB-1, PCNA, HPV 16 and p53 as diagnostic markers for cervical intraepithelial neoplasia.

The present investigation evaluated the relationship between dysplasia of the uterine cervix and telomerase activity, expression of p53, MIB-1 and PCNA. Telomerase activity was measured on cervical cytobrush material from 126 women suspected of having dysplasia and 61 controls using the telomeric repeat amplification protocol. Immunohistochemistry was used to detect the tumor suppressor protein p53 and cell proliferation, the latter by MIB-1 and PCNA expression. Infection with human papillomavirus 16 was detected by PCR amplification and Southern blot hybridization of DNA extracted from the same brush material. Positive telomerase activity was found in 5 of 43 (11.6%) normal samples, 12 of 57 (21.1%) samples with inflammation or koilocytosis, 7 of 17 (41.2%) CIN 1 (cervical intraepithelial neoplasia, grade 1), 8 of 20 (40.0%) CIN 2, and 25 of 42 (59.5%) CIN 3/ CIS. Telomerase activity was significantly related to the level of dysplasia (p<0.001) and proliferation measured by MIB-1 (p=0.019), but not to the level of PCNA (p=0.445), HPV 16 status (p=0.098) or staining for p53 (p=0.271). Dysplasia was also related to PCNA, MIB1, p53, and presence of HPV 16. A sequential increase in the examined parameters, paralleling the progression of abnormality, was observed. PCNA and telomerase showed an increase in CIN 1, MIB-1 and HPV16 in CIN 2, and finally p53 in CIN 3/CIS.

A simple one-stop menstrual problem clinic with use of hysterosonography for the diagnosis of abnormal uterine bleeding.

BACKGROUND: The purpose of the present study was to evaluate a one-stop outpatient bleeding disorder clinic in a Scandinavian population. METHODS: One hundred and fourteen women under the age of 60 years referred to the clinic for bleeding disorders. The consultation included pelvic ultrasound, hysterosonography and, when indicated, endometrial sampling. RESULTS: In 93% of the patients a sufficient diagnosis of the uterine cavity was attained at a one-stop visit. Eighty-six percent of the patients were investigated according to the one-stop program, and in 73% of the patients a treatment plan could be formulated during the consultation. Twenty-one percent had selective resection of intracavitary abnormalities. In 3% no intracavitary abnormality was found at hysteroscopy, even though hysterosonography had indicated this. CONCLUSIONS: Most patients under the age of 60 with bleeding disorders can be investigated by a one-stop out-patient procedure with the use of hysterosonography and endometrial sampling. Diagnostic or operative hysteroscopy was needed in cases of insufficient hysterosonography and suspicion of intracavitary abnormalities. This procedure can assist in determining the therapeutic approach and can often lessen the extent of surgical intervention or obviate it altogether.

Length tension relationships in the nonpregnant and pregnant rat uterus and the effect of antiprogestin.

Length-tension relationships and the tissue composition of the corpus and the cervix uteri were investigated in a rat model. Four groups of rats were used: nonpregnant (n = 12); day 18 of pregnancy treated with vehicle (n = 8); day 18 of pregnancy treated with the antiprogestin ZK 98 299 (Onapristone) for 19 h (n = 8); and day 22 of pregnancy during spontaneous labour (n = 8). Increased extensibility and maximal contractility in both corpus and cervix uteri were demonstrated with increased gestational age. The collagen concentration was reduced significantly in corporal preparations from pregnant rats compared with those from nonpregnant rats but not in specimens from the cervix. Antiprogestin treatment tended to increase the contractile ability.

Mast cells in cervical ripening--an immunohistochemical and biomechanical study in rats.

Cervical ripening purportedly involves different cell types and mediators normally associated with inflammatory reactions. The purpose of the present study was to determine the presence of mast cells in rat cervices during spontaneous and antigestagen induced ripening and to test whether a mast cell stabilizer was able to inhibit the antigestagen induced cervical ripening. Immunohistochemical examinations demonstrated an increased number of mast cells in pregnant and intrapartum rats. Furthermore, mast cell degranulation was found to be prominent after antigestagen treatment. The degranulation was completely abolished by co-treatment with the mast cell stabilizer. Biomechanical analysis showed that the mast cell stabilizer also inhibited the antigestagen induced cervical ripening to some extent. Thus, it is concluded that mast cell stabilizers might constitute a new approach in the treatment of preterm cervical ripening.

Eosinophils in human cervical ripening.

OBJECTIVE: Cervical ripening has many similarities to an inflammatory reaction. Eosinophil granulocytes are involved in several inflammatory responses. The objective was to investigate the presence of eosinophils in human cervix uteri during different conditions. STUDY DESIGN: Cervical biopsies were obtained from non-pregnant (n = 6), women in early pregnancy (n = 11) and from three groups of women at term: spontaneous vaginal deliveries (n = 5); vaginal deliveries after pretreatment with Prostaglandin E2 (n = 7); and from women who underwent planned Caesarean section (n = 7). Immunohistochemical staining for eosinophil granulocytes (ECP, EG2) were performed. The biopsies were analysed blinded. RESULTS: Eosinophils showing degranulation in the tissue were found in all specimens from vaginal deliveries. No eosinophils, or very few were seen in the biopsies from non-pregnant, early pregnant women or planned caesarean section. Prostaglandin treatment had no effect on the results. CONCLUSION: Eosinophils participate in cervical ripening at term in women, and seem to arise mainly after labour.

[Phantom breast syndrome]. / Fantombrystsyndromet.

Phantom breast syndrome following mastectomy has been reported by other authors. However, the temporal course, character and extent of this phenomena have not been elucidated. In a prospective study we have investigated the incidence, clinical picture and temporal course of phantom breast syndrome. One hundred and twenty women who started postoperative control or treatment at the Oncology Department over a one-year period were interviewed by a standard questionnaire three weeks after the operation. One year later 110 patients and six years later 68 patients were interviewed again. The incidence of phantom pain and non-painful phantom sensations was respectively 13.3% and 15.0%, respectively three weeks after the mastectomy. 12.7% and 11.8% after one year, and 17.4% and 11.8% after six years. A significant relationship between preoperative pain and phantom breast syndrome was found, but neither age, cancer treatment or postoperative sequelae seemed to affect the occurrence of phantom breast syndrome. Scar pain was found to persist in 30.9% of the patients six years after the operation. The present incidence of phantom-related phenomena is close to the incidence reported by others. However, persistent phantom pain after mastectomy may be more common than usually expected. Also, the persistence of scar pain seems to be more common than generally expected.

Biomechanical analysis of cervix uteri in nonpregnant, pregnant and antigestagen (ZK 98 299) treated pregnant rats.

The biomechanical properties of the cervix uteri of the rat were studied under different pharmacological conditions. Four groups of rats were enrolled: A. non-pregnant (N = 12), B. 18 days pregnant treated with vehicle (N = 14), C. 18 days pregnant treated with the antigestagen ZK 98 299 (Onapristone) for 19 hours (N = 15), D. 22 days pregnant during spontaneous labor (N = 12). Load-dimension curves of two 2 mm ring-preparations from each cervix were obtained by a material testing machine. The results showed that the sampling position, the cervical ripening process, and the influence of antigestagen treatment were reflected in the biomechanical and compositional parameters. In conclusion the methodology in the present study constitute a model in which the effect of pharmaca on cervical ripening can be tested. The study demonstrated that antigestagen treatment induced biomechanical changes in the cervix comparable to those occurring during physiological cervical ripening at term.