Cross-sectional study for derivation of a cut-off value for identification of an early versus delayed diagnosis of endometriosis based on analytical and descriptive research methods.

BACKGROUND: Endometriosis is a benign, hormone-dependent, chronic inflammatory gynecological disease accompanied by cyclic and acyclic pelvic pain and other complaints. The long lists of research recommendations in the AWMF guideline (Burghaus et al., Geburtshilfe Frauenheilkd 81:422-46, 2021) and ESHRE Endometriosis Guideline (ESHRE Endometriosis Guideline Development Group, Endometriosis: Guideline of European Society of Human Reproduction and Embryology, 2022) show that there is still a great need for research in all aspects of the disease. Diagnostic delay, defined as the mean time between symptom onset and confirmed diagnosis, is a particular problem associated with endometriosis. Some quantitative and qualitative studies have investigated possible reasons for this. A range of physician-related (Dixon et al., Br J Gen Pract 71:e668-e676, 2021; van der Zanden and Nap, Reprod Biomed Online 32:527-31, 2016) and patient-related factors (Sayer-Jones and Sherman, Health Psychol Behav Med 9:456-79, 2021) as well as stigmatization of the topic of menstruation by society have been identified (Kruckenberg, Frauenarzt 59:2-5, 2018; Seear, Soc Sci Med 69:1220-7, 2009). The consequences of the disease being diagnosed late (or too late) on the course of disease, the quality of life and the costs of the disease have already been documented in studies (Sims Int J Environ Res Public Health 18(15):8210, 2021; Surrey Adv Ther 37:1087-99, 2020). However, a systematically derived cut-off value that clearly distinguishes between short and long delay is still lacking. Therefore, the aim of our study was to derive a threshold value for the definition of a target corridor for endometriosis diagnosis based on descriptive and analytical methods. METHODS: Since our review of the rather sparse publications on diagnostic delay did not yield satisfactory results, we used descriptive statistics and location parameters to calculate a cut-off value for German population data from the EndoCost study. Statistical methods were used for correlation analysis of shortDD versus longDD (correlation analysis and logistic regression) and group membership (discriminant analysis). RESULTS: Five years was identified as the cut-off value that significantly differentiated between shortDD and longDD based on various disease-related variables. This suggests that endometriosis should be definitively diagnosed within less than five years to minimize the risk of an unfavorable course of the disease. CONCLUSION: Our findings confirmed that an early onset of endometriosis-related symptoms is the most important risk factor for a long diagnostic delay. Consequently, adolescent females should receive increased attention as an especially vulnerable group. Evidently, there is an urgent need to develop adequate concepts to improve the endometriosis education and care among this target group.

The impact of the COVID-19 pandemic on women seeking fertility treatment: the patient's perspective.

PURPOSE: This study sought the views of women with impaired fertility on the impact of the COVID-19 pandemic on their fertility treatment and psychological wellbeing. METHODS: A cross-sectional, anonymous, online questionnaire was completed in June-December 2020 by 249 women attending fertility clinics across Germany. All women seeking treatment in fertility clinics were eligible to participate. The online survey covered questions about the patient's quality of life, their opinions about the professional societies' recommendations and their effects as well as any concerns about infection with SARS-CoV-2. RESULTS: Three-quarters of participants disagreed with the pausing of fertility treatments. Women who participated from October to December 2020, when the incidence rate was high, were as likely to disagree as participants that participated from June to September 2020 (73% vs 79%, p = 0.3). Seventy-two participants (29%) had their appointments cancelled. Nearly all (97%) reported being upset by this, with 40 (56%) reporting that they were extremely or very disappointed about the cancellation. Women who had to wait 10 weeks or longer were more likely to be upset by the postponement or cancellation of their appointment than women who had to wait a shorter amount of time (p = 0.01). Many participants (41%) were worried about possible negative effects a SARS-CoV-2 infection might have related to their fertility, pregnancy or unborn child. CONCLUSION: Postponement of treatments increased distress among patients and should be avoided when possible. Fertility clinics must provide information about the current state of knowledge of SARS-CoV-2 infections in pregnancies and options for immunization.

Pregnancy Outcomes After Transcervical Radiofrequency Ablation of Uterine Fibroids with the Sonata System.

Objective: To describe pregnancy outcomes in women who conceived after undergoing transcervical fibroid ablation (TFA) as treatment for symptomatic uterine fibroids. Materials and Methods: TFA was used to treat symptomatic uterine fibroids with radiofrequency energy, both under clinical trial protocol and commercial usage in hospitals in Europe, the United Kingdom, Mexico, and the United States. All women who reported pregnancies to their physicians after undergoing TFA with the Sonata® System and provided consent for use of their data were included. Results: There have been 36 pregnancies representing 20 deliveries among 28 women who were treated with TFA. Five women conceived more than once postablation, and four conceived as a result of assisted reproductive technology (ART). Outcomes include 8 vaginal deliveries, 12 Cesarean sections, 3 therapeutic abortions, and 8 first trimester spontaneous abortions (four occurring in a patient with a history of recurrent pregnancy loss and an immunologic disorder). Five women are currently pregnant, two of whom previously delivered after TFA. There were no 5-minute Apgar scores <7, and all neonates weighed >2500 g. All deliveries occurred at ≥37 weeks except for one delivery at 35 6/7 weeks. There were no uterine ruptures or abnormal placentation and no reports of postpartum hemorrhage or stillbirths. Ablated fibroids included transmural, submucous, and intramural myomata up to 7 cm in diameter. Conclusions: Normal pregnancy outcomes at term have occurred after TFA with the Sonata System, including in women with recurrent abortion and in those undergoing ART. There were no instances of low Apgar scores, low birthweight, stillbirth, postpartum hemorrhage, or uterine rupture (FAST-EU, NCT01226290; SONATA, NCT02228174; SAGE, NCT03 118037). (J GYNECOL SURG 38:207).

Cognitive function in association with high estradiol levels resulting from fertility treatment.

The putative association between hormones and cognitive performance is controversial. While there is evidence that estradiol plays a neuroprotective role, hormone treatment has not been shown to improve cognitive performance. Current research is flawed by the evaluation of combined hormonal effects throughout the menstrual cycle or in the menopausal transition. The stimulation phase of a fertility treatment offers a unique model to study the effect of estradiol on cognitive function. This quasi-experimental observational study is based on data from 44 women receiving IVF in Zurich, Switzerland. We assessed visuospatial working memory, attention, cognitive bias, and hormone levels at the beginning and at the end of the stimulation phase of ovarian superstimulation as part of a fertility treatment. In addition to inter-individual differences, we examined intra-individual change over time (within-subject effects). The substantial increases in estradiol levels resulting from fertility treatment did not relate to any considerable change in cognitive functioning. As the tests applied represent a broad variety of cognitive functions on different levels of complexity and with various brain regions involved, we can conclude that estradiol does not show a significant short-term effect on cognitive function.

Reproductive capacity and recurrence of disease after surgery for moderate and severe endometriosis - a retrospective single center analysis.

BACKGROUND: Endometriosis can be associated with considerable pain and sterility. After surgical excision of moderate or severe endometriosis lesions, the rate of recurrence reaches up to 67%. The objective of this retrospective study was to establish the recurrence and pregnancy rates following surgical resection of stage III/IV endometriosis lesions. Indications for operation were endometriosis symptoms, sonographic findings and/or infertility. METHODS: A total of 456 patients who underwent stage III/IV endometriosis surgery between 2004 and 2014 were sent a questionnaire relating to their postoperative medical treatment, pregnancies, relief of symptoms and recurrence. Responses of 206 patients (45.2%) and their clinical data were analysed for this study. RESULTS: A total of 66.5% (N = 137) of patients had stage III disease, and 33.5% (N = 69) had stage IV disease. The average age was 37 years (17-59). A total of 63.1% (N = 130) of surgeries were performed by laparoscopy, 21.8% (N = 45) were performed by laparotomy and 15% (N = 31) were performed by conversion. Complete resection of endometriosis lesions was achieved in 90.8% of patients (N = 187). After surgery, 48.5% (N = 100) of the women did not receive hormonal treatment; the main reason was the desire for children in 53%. Complete or partial relief in complaints was achieved in 93.2% (N = 192). The rate of recurrence was 21.8% (N = 45). The statistically significant factors that was associated with a higher risk to develop recurrence was an age < 35 (p < 0.005). After surgery, 65.8% (79/120) of patients who wished to have children became pregnant. There was a statistically significant association among a higher postoperative pregnancy rate and age < 35 (p < 0.003) in multivariate logistic regression analysis and laparoscopic surgical access in univariate logistic regression analysis (p < 0.01). CONCLUSION: We assessed the high percentage of complete or partial relief of symptoms of 93.2%, the high postoperative pregnancy rate of 65.8% and the low rate of recurrence of 21.8% compared to international literature to be very encouraging for women suffering from moderate and severe endometriosis. Though laparoscopy is considered the 'gold standard'of endometriosis surgery, laparotomy still may be indicated in patients with extensive endometriosis especially to preserve reproductive function.

Effects of Intranasal Oxytocin Administration on Sexual Functions in Healthy Women: A Laboratory Paradigm.

PURPOSE: The neuropeptide oxytocin (OXT) has a variety of physiological functions in maternal behavior and attachment including sexual behavior. Based on animal research and our previous human studies, we set out to investigate intranasal administration of OXT and hypothesized that OXT should be able to modulate sexual function in women. METHODS: In a double-blind, placebo-controlled, crossover laboratory setting, the acute effects of intranasal administered OXT (24 international units) on sexual drive, arousal, orgasm, and refractory aspects of sexual behavior were analyzed in 27 healthy females (mean age ± SD, 27.52 ± 8.04) together with physiological parameters using vaginal photoplethysmography. FINDINGS: Oxytocin administration showed no effect on subjective sexual parameters (eg, postorgasmic tension; P = 0.051). Physiological parameters (vaginal photoplethysmography amplitude and vaginal blood volume) showed a response pattern towards sexual arousal but were not affected by OXT. IMPLICATIONS: Using a well-established laboratory paradigm, we did not find that intranasal OXT influences female sexual parameters. Also, sexual drive and other functions were not affected by OXT. These findings indicate that OXT is not able to significantly increase subjective and objective parameters of sexual function in a setting with high internal validity; however, this might be different in a more naturalistic setting.

Neonatal and Maternal Short-Term Outcome Parameters in Instrument-Assisted Vaginal Delivery Compared to Second Stage Cesarean Section in Labour: A Retrospective 11-Year Analysis.

BACKGROUND: This study is aimed at comparing the neonatal and maternal short-term outcomes after instrumental-assisted vaginal delivery and cesarean section (CS) in labour. METHODS: This retrospective study over a period of 11 years included singleton pregnancies above 34 + 0 gestational weeks, giving birth either by instrumental-assisted delivery or CS in labour. Maternal and neonatal outcome parameters were analysed using t test or linear regression. RESULTS: A total of 1,971/2,571 deliveries were included for analysis: 149 forceps-, 393 vacuum-assisted deliveries and 1,420 CS in labour. Regarding maternal outcome, the rate of severe anaemia and hemorrhage in women who delivered by CS in labour was lower than in instrumental-assisted delivery. Analysis of neonatal outcome parameters showed a lower cord pH <7.20 in CS; however, 5-min Apgar score and the need for intervention did not differ with the mode of delivery. The mode of anaesthesia affected the neonatal recovery rate. Subanalysis within instrumental deliveries showed reduced rates of vaginal tears, but higher rates of episiotomy in forceps-assisted deliveries. Except for higher rates of cephalhaematomas after ventouse, no differences were detected regarding further neonatal outcome measures. CONCLUSION: Assuming that indication and application is correct, vaginal instrumental-assisted delivery can be considered as an alternative delivery mode to second stage CS in labour.

Peri- and postoperative management and outcomes of morbidly obese patients (BMI > 40 kg/m2) with gynaecological disease.

INTRODUCTION: For the last two decades, obesity rates have been increasing in both developed and developing countries, with the number of obese women roughly doubling during this period (Stevens et al. in Popul Health Metr 10(1):33, 2012). Obesity represents one of the biggest epidemics of the 21st century. The aim of this retrospective study is to characterise the outcomes of gynaecologic surgeries in cases of extremely obese women with a body mass index (BMI) over 40 kg/m2. METHODS: This study is a retrospective case control study in a single-centre setting. Our clinical database was searched for gynaecological operations performed on morbidly obese patients (BMI > 40 kg/m2) between 2009 and 2014 in the Department of Gynaecology and Obstetrics at Hannover Medical School. We matched these results with random patients of normal body weight who had similar surgical procedures and diseases. RESULTS: We included 97 obese patients in our case group and 99 patients in the control group. We found an association between a strongly elevated BMI and peri- and postoperative morbidity. Both intraoperative and postoperative complications are significantly increased in morbid obesity with a BMI over > 40 kg/m2. We observed intraoperative complications in 55.6% and postoperative complications in 50.5% of patients with extreme obesity. In contrast, the complication rate in the control group with a normal BMI was 11% intraoperatively (p = 0.0001) and 3% postoperatively (p = 0.0001). The data showed that perioperative and postoperative morbidity could be reduced by laparoscopic surgery in many cases, with a significant lower rate of difficulties with closing the wound, a significant shorter duration of surgery and a significant lower rate of infections combined with a significant lower reoperation rate and shorter hospital stay. In gynaecological-oncological diseases, we could demonstrate a reduced radicality during the operative procedure due to extreme obesity. DISCUSSION: Dealing with the growing number of obese patients is essential, because the problems emerging from obesity are manifold for the treating hospitals as well as the general health system. For this high-risk patient group, it is indispensable to obtain a thorough overview of the patient's overall situation preoperatively to ensure good perioperative care and complications management.

Gestational diabetes mellitus: an evaluation of gynecologists' knowledge of guidelines and counseling behavior.

PURPOSE: Knowledge of risks, adequate pre- and post-partum care, and counseling is essential to reduce short- and long-term consequences for women with gestational diabetes mellitus (GDM) and their offspring. Our study explored the current GDM guideline knowledge and practiced patient counseling of private gynecologists in Germany. METHODS: A survey assessing the GDM guidelines and patient counseling was mailed to 775 practicing gynecologists. We evaluated the knowledge of maternal and offspring disease risks, counseling practice, and guideline awareness. Descriptive statistics were used to analyze the responses and Chi-Square or Fisher exact test to explore differences between groups. RESULTS: Of the 418 private gynecologists (54.1 % response rate) who responded, the majority was aware of obesity and GDM in the previous pregnancy as risk factors for GDM. To a lesser extent, risk factors like recurrent miscarriages and stillbirth were recalled. Eighty percent stated that GDM was associated with a higher risk for the development for hypertension and 96 % with type 2 diabetes in the mother. Respondents with knowledge of the current GDM guidelines were more often aware of the development of chronic diseases, counseled patients more frequently, and performed post-partum glucose screenings more regularly compared with private gynecologists with no knowledge of the guidelines. CONCLUSIONS: The majority of participants incorporated recent recommendations into their practice patterns for GDM. Providing private gynecologists with additional training may further improve care for women with GDM-affected pregnancies.

Clinical diagnosis and therapy of uterine scar defects after caesarean section in non-pregnant women.

PURPOSE: Caesarean delivery (c-section) scar dehiscences may cause bleeding abnormalities, e.g. postmenstrual spotting, dysmenorrhea and abdominal pain, secondary sterility and at worst peripartum uterine rupture. The purpose of this study was firstly to identify the correlation of women's complaints after c-section with scar-related clinical symptoms. Secondly, the effects of corrective surgery on preoperatively existing complaints were analysed and assessed in the patient population of our clinic. METHODS: We present data of a retrospective study of 13 premenopausal, non-pregnant women with symptomatic c-section scars. In 9 out of 13 patients, a microsurgical uterus reconstruction was performed by mini-laparotomy. The postoperative changes of scar-associated symptoms were assessed by a questionnaire as earliest as 4 months after surgery (N = 5). RESULTS: The c-section scar was visualised by transvaginal sonography in 12 out of 13 women by a typical U- or V-shaped hypoechoic or anechoic fluid accumulation in the region of former uterotomy and in all 13 patients by hysteroscopy. Bleeding disorders were often accompanied by dysmenorrhea/abdominal pain (38.5%, N = 5) and secondary sterility (46.2%, N = 6). Blood residues in the scar pouch and bleeding disorders/postmenstrual spotting were found in 30.8% of patients (N = 4) and combined with secondary sterility in 38.5% of patients (N = 5). Reconstructive surgeries resulted in discontinuation of bleeding disorders in all women and a pregnancy in three out of five patients (60%) with secondary sterility. CONCLUSION: Clinical symptoms, e.g. "bleeding disorders" like postmenstrual spotting, "pain/dysmenorrhea" and "secondary sterility" could be specific indicators for the diagnosis of uterine dehiscence after c-section. Scar dehiscences can be diagnosed by obtaining the patients medical history and asking for typical symptoms followed by vaginal sonography and diagnostic hysteroscopy. If a c-section scar defect is confirmed, microsurgical uterus reconstruction can stop postmenstrual spotting, reduce abdominal pain/dysmenorrhea and improve fertility.

Preeclampsia and long-term risk of cardiovascular disease: what do obstetrician-gynecologists know?

BACKGROUND: Preeclampsia (PE), a hypertensive disorder of pregnancy affects 2-8% of women and is associated with increased cardiovascular disease (CVD) risk later in life. There is little information about the knowledge of obstetrician-gynecologists in German outpatient care setting regarding the future health risk of PE and knowledge of the current guidelines on treatment and counseling patients post PE. This study aimed to assess whether obstetrician-gynecologists are aware of PE's association with maternal long-term adverse outcomes and providing appropriate counseling. METHODS: A random sample of 500 obstetrician-gynecologists in the federal state of Lower Saxony was mailed a survey and a reminder with a second copy of the survey. The questionnaire elicited both personal information, and knowledge on future disease risks, e.g. cardiovascular disease (CVD) and current guidelines as well as on counseling practice. Descriptive analysis was used to analyze the responses. RESULTS: A total of 212 obstetrician-gynecologists (42.4%) responded to the questionnaire. A large proportion of physicians stated that PE was associated with a higher risk for the development for hypertension (86.6%), stroke (78.5%) and kidney disease (78.0%). Of the participants 75.8% reported that women after PE have a shorter life expectancy. Respondents with knowledge of the current guidelines of the German Association of Obstetrics and Gynecology concerning follow up and risk management of PE (45.2%) were more often aware of the development of CVD and stroke and counseled patients on self -blood-pressure measurement, meaning and long-term-risks of PE and attached importance to family history of PE compared to physicians with no knowledge of the guidelines. CONCLUSION: Although the majority of obstetrician-gynecologists were aware of higher CVD risk after PE, weaknesses exist in the follow up care and counseling of these patients. These deficiencies would be amendable to directed educational activities to improve the implementation of current guidelines.

Fear of fertility side effects is a major cause for COVID-19 vaccine hesitance in infertile patients.

Introduction: This study aims to investigate the acceptance, hesitance and attitudes of infertile female patients toward the COVID-19 vaccination. Methods: An anonymous cross-sectional online survey was conducted between 28th of January to 10th of August 2022. The questionnaire consisted of 35 questions on demographics, COVID-19 vaccination status, prior concerns of the vaccinated participants and reasons for not vaccinating among unvaccinated participants, and factors influencing the decision not to vaccinate. Results: Of 406 participants who answered all questions, 92.1% reported having received at least one dose of COVID-19 vaccine, 7.9% were unvaccinated. Factors associated with the decision for vaccination were full time or part time employment (p = 0.05), high trust in the principle of vaccination (p < 0.001), high willingness for other vaccination during fertility treatment (p < 0.001) and risk factors for severe COVID-19 (p = 0.007). Concerns about directly occurring adverse effects after vaccination (42.0%), about impact on own fertility (21.9%) or on the fertility treatment (27.5%) were the main concerns beforehand of vaccinated participants. Correlations between fertility concerns and mistrust in the general principle of vaccination were found. Beside general health concerns, unvaccinated participants reported fears about fertility impairment as the most important arguments against a COVID-19 vaccination (median of 5.0 on a five-point-Likert scale). Conclusion: Both vaccinated and unvaccinated participants stated having concerns and fears about side effects of the COVID-19 vaccination on their fertility. To increase patients' trust in medical recommendations, such as vaccination, to avoid mistrust in the medical system and to maintain patient's compliance, there should be additional educational services that address infertile patients and their needs.

High prevalence of reduced fertility and use of assisted reproductive technology in a German cohort of patients with peripartum cardiomyopathy.

BACKGROUND: Over the past decades the use of assisted reproduction technology (ART) increased worldwide. ARTs are associated with an elevated risk for cardiovascular complications. However, a potential relation between subfertility/ARTs and the heart disease peripartum cardiomyopathy (PPCM) has not been systematically analyzed yet. METHODS: A retrospective cohort study was carried out, including n = 111 PPCM patients from the German PPCM registry. Data from PPCM patients were compared to those from postpartum women in the German general population. RESULTS: The prevalence of reported subfertility was high among PPCM patients (30%; 33/111). Most of the subfertile PPCM patients (55%; 18/33) obtained vitro fertilizations (IVF) or intracytoplasmic sperm injections (ICSI). PPCM patients were older (p < 0.0001), the percentage of born infants conceived by IVF/ICSI was higher (p < 0.0001) with a higher multiple birth (p < 0.0001), C-section (p < 0.0001) and preeclampsia rate (p < 0.0001), compared to postpartum women. The cardiac outcome was comparable between subfertile and fertile PPCM patients. Whole exome sequencing in a subset of n = 15 subfertile PPCM patients revealed that 33% (5/15) carried pathogenic or likely pathogenic gene variants associated with cardiomyopathies and/or cancer predisposition syndrome. CONCLUSIONS: Subfertility occurred frequently among PPCM patients and was associated with increased age, hormonal disorders, higher twin pregnancy rate and high prevalence of pathogenic gene variants suggesting a causal relationship between subfertility and PPCM. Although this study found no evidence that the ART treatment per se increases the risk for PPCM or the risk for an adverse outcome, women with subfertility should be closely monitored for signs of peripartum heart failure.

Clinical characterisation of women with persistent genital arousal disorder: the iPGAD-study.

Persistent Genital Arousal Disorder (PGAD) is a rare condition-mostly in women-where patients perceive prolonged genital arousal without any sexual desire or stimulation. Etiopathological considerations reach from peripheral to central issues over local disturbance of the pudendal nerve to neuropathy, psychosocial, and pharmacological theories. Since well controlled clinical studies about PGAD in conjunction with a mental and somatic health status are missing, this study is a detailed clinical investigation of PGAD patients compared to healthy controls. 26 women who fulfilled diagnostic criteria for PGAD were compared to 26 age matched healthy controls. Investigations included comparison of vegetative, gynaecological and sexual history, psychiatric features as well as a (neuro-)radiological, neurophysiological and gynaecological examination. Moreover, a detailed clinical characterisation of PGAD symptoms was performed. PGAD symptoms were mostly characterised as tingling or prickling and were permanently present. In over 80%, PGAD symptoms were located in the clitoris. Almost 70% reported radiations to other regions of the body. Most frequent trigger factors were tight clothes, mental stress, driving a car/bus/bicycle and sexual intercourse. Relieving factors were mainly distraction, relaxation, physical exercise, masturbation and swimming. In group comparisons, PGAD presented with significant higher rates of sexual dysfunctions, spontaneous orgasms, swelling of the genitals, extraordinary lubrication as well as higher rates in depression, agoraphobia, generalized anxiety disorder and lifetime panic disorder. Significantly more PGAD patients were diagnosed with restless legs symptoms. In contrast childhood traumatization, somatization disorder, suicidality, gynaecological as well as neurophysiological examination of the pudendal nerve were not different between the groups. MRI of the brain, pelvis and spinal cord was unsuspicious and incidental findings - including Tarlov cysts or pelvic venous congestion - were equally distributed among the groups. In summary, our study provides a careful characterization of women with PGAD highlighting a serious mental burden, most probably as a consequence of PGAD. With the current set of clinical investigations there was no evidence of a clear causal relationship to a specific clinical finding as it has been previously discussed. Future studies and additional techniques will have to further explore where and how in the peripheral or central nervous systems PGAD develops.

Mitomycin C in combination with vinorelbine in anthracycline- and/or taxane-pretreated patients with metastatic breast cancer.

BACKGROUND: Patients with metastatic breast cancer (MBC) with disease progression after anthracycline-and/or taxane-containing therapy need an effective drug regimen with low toxicity. Mitomycin C (MMC) and vinorelbine (VNR) are suitable candidates for combination therapy in the second-/third-line treatment of MBC. This study evaluates the safety and efficacy of an MMC/VNR combination chemotherapy in pretreated patients with MBC. PATIENTS AND METHODS: In a phase II trial, patients with anthracycline-and/or taxane-pretreated MBC were treated with MMC 8 mg/m(2) (day 1) and VNR 25 mg/m(2) (days 1 and 8) every 4 weeks for up to 6 cycles or until disease progression. RESULTS: In 51 eligible patients, 13 (26%) partial remissions (PRs), 20 (39%) stable diseases (SDs) and 18 (35%) progressive diseases (PDs) were observed. The median progression-free survival (PFS) was 5.0 months. The main grade 3/4 toxicities were neutrocytopenia (41%), granulocytopenia (37%), and thrombocytopenia (4%). Other hematological and non-hematological toxicities were mostly mild. CONCLUSION: The combination of MMC and VNR is an effective and relatively well-tolerated regimen for anthracycline- and/or taxane-pretreated patients with MBC and is suitable for outpatient therapy.

Aromatase inhibitors as solely treatment in postmenopausal breast cancer patients.

Several studies evaluating the clinical effectiveness of endocrine therapy alone in breast cancer patients aged 70 years or older reported comparable survival rates to conventional surgical therapy, although the incidence of local recurrences was higher. Primary endocrine therapy is therefore only recommended as an alternative approach in elderly woman with estrogen receptor positive tumors who are deemed inoperable or who refuse surgery. We report our experience with aromatase inhibitors as primary endocrine therapy for estrogen receptor positive breast cancer in postmenopausal woman who are impaired by other diseases, refuse surgery or are of old age. Fifty-six patients with fifty-seven ER+ operable breast cancers who refused surgery, were judged ineligible for surgery because of comorbidity, or were of old age were treated with endocrine therapy using aromatase inhibitors only. Digital mammography and high-end breast ultrasound were used to assess tumor sizes. The mean age of the patients was 74 years (range 52-102 years). All patients suffered from breast cancer. The mean follow-up interval was 40 months (range 5-92 months). Seven patients (12%) achieved complete clinical remission, 31 (57%) partial response giving an overall objective response rate of 69%. In addition, seven (12%) patients showed stable disease, giving a clinical benefit rate (complete remission + partial response + stable disease rate) of 81%. Eleven patients (19%) progressed after an initial partial response or stable disease. Only one patient (2%) progressed on endocrine therapy within the first months. Eventually, 22 (39%) patients underwent surgery after informed consent to achieve better local tumor control. Primary endocrine therapy with aromatase inhibitors may offer an effective and safe alternative to surgery giving a high local control rate in postmenopausal women who refuse surgery, who are judged ineligible for surgery, or are of old age.

The risk of ectopic pregnancy following tubal reconstructive microsurgery and assisted reproductive technology procedures.

PURPOSE: The incidence of ectopic pregnancy (EP) in the general population is 2%, whereas the EP rate following assisted reproductive technologies (ART) is between 2.1 and 11%. EP is also an adverse effect of tubal surgery with incidences up to 40% depending on the type, location, and severity of tubal disease and the surgical procedure. METHODS: This paper looks at the incidence of EP following tubal reconstructive microsurgery, analyzes risk factors for EP following own 1,295 ART cycles and looks on the incidence of EP in 128,314 pregnancies following ART according to the presence or absence of tubal infertility using data from the German IVF Registry (DIR). RESULTS: In our clinic, the EP rate following resterilization was 6.7%. In the presence of acquired tubal disease, the EP rate following adhesiolysis, salpingostomy, salpingoneostomy, fimbrioplasty, and anastomosis was 7.9%. The EP rate following ART in our clinic was 5.6%. Previous abdominal surgeries, microsurgical procedures, hydro-/sactosalpinges, salpingitis, salpingitis isthmica nodosa, and periadnexal adhesions showed a significant positive correlation with EP as outcome. Data of DIR demonstrate a significantly increased incidence of EP in the presence of tubal pathology. The highest EP rate related to all clinical pregnancies was 4.5% (95% CI 3.0-6.0) in smoking women <30 years with tubal pathology following IVF. CONCLUSIONS: In the presence of tubal infertility, the incidence of EP following ART and tubal microsurgery are approximately comparable with each other and higher than in women without tubal infertility. The success of infertility surgery depends on a careful selection of appropriate patients.

Diagnostic challenges of hemihematocolpos and dysmenorrhea in adolescents: obstructed hemivagina, didelphys or bicornuate uterus and renal aplasia is a rare female genital malformation.

OBJECTIVES: To develop a clear diagnostic and therapeutic strategy for adolescents presenting with abdominal pain and vaginal tumor caused by congenital female genital anomalies, such as blind hemivagina and uterine anomalies, as the lack of the correct diagnosis of the underlying anatomical genitourinary malformation frequently leads to destructive surgical procedures. METHODS: Retrospective study, study group: patients with double/bicornuate uterus, blind hemivagina and hematocolpos (n = 13), controls: patients with uterine malformation and complete vertical vaginal septum (n = 11), analysis for: menarche, age at onset of symptoms, type of malformation, symptoms leading to admission and diagnostic/surgical techniques applied. RESULTS: Median age at diagnosis study group 19.85 (SD ± 6.23, range 13-23 years) versus controls 26.09 years (SD ± 7.44, 16-36 years); predominance of imperforated hemivagina: 69.2 % right-sided versus 30.8 % left-sided septum; renal agenesis ipsilateral to imperforate hemivagina 100 % study group versus 9.1 % controls; 84.6 % previous surgical interventions in the study group, such as partial removal of the septum and re-obliteration, unilateral salpingo-ovarectomy and vaginal drainage of pyometra. We used a single transvaginal surgical procedure, including removal of the obstructed vaginal septum and marsupialization of the blind hemivagina. CONCLUSIONS: A diagnostic and therapeutic algorithm for young women presenting with progressive dysmenorrhea and abdominal pain and/or vaginal tumor reduces destructive interventions.

The First Description of Docetaxel-Induced Recall Inflammatory Skin Reaction After Previous Drug Extravasation.

OBJECTIVE: To describe a cutaneous recall soft tissue injury at the site of previous extravasation of docetaxel. CASE SUMMARY: A 65-year-old white female with an invasive ductal carcinoma of the right breast was treated with carboplatin AUC 2 and docetaxel 30 mg/m(2) weekly via a peripheral vein access. During the 14th cycle, drug extravasation of docetaxel occurred in the left antecubital fossa characterized by a mild erythema without edema. A severe erythema developed in the former area of extravasation after the 15th cycle of carboplatin/docetaxel. The recall dermatitis continued to exacerbate after each course of systemic docetaxel chemotherapy and finally led to termination of this therapy. DISCUSSION: In general, extravasation of docetaxel causes only mild local skin reactions without further necessity of intervention. For pegylated liposomal doxorubicin and paclitaxel, inflammatory recall phenomena at sites of previous drug extravasation are rare and often occur as single events following administration of the same cytotoxic drug. According to the Naranjo probability scale, the administration of docetaxel in this case probably led to the cutaneous soft tissue injury as a result of extravasation. CONCLUSIONS: Caution is needed after an episode of docetaxel extravasation. Even after a therapy interruption of several weeks, resumption of chemotherapy with docetaxel might lead to recrudescence of the inflammatory skin reaction.

Is there still a role for reconstructive microsurgery in tubal infertility?

PURPOSE OF REVIEW: To review the current role of tubal reconstructive surgery in the era of assisted reproductive techniques (ARTs). RECENT FINDINGS: After tubal reconstructive surgery, couples may have unlimited attempts to conceive naturally. Operative risks are low; the risk for ectopic pregnancy after surgery is 4-10%. ART is associated with a number of potential complications: severe ovarian hyperstimulation syndrome (0.25-2%), multiple pregnancies (up to 25%), a higher rate of major malformations and stillbirths, and ectopic pregnancy (1-13%). Birth rates following ART differ between 19 and 35%, depending on different laws governing the fertilization of a limited number of oocytes and the number of embryos transferred. Resterilization is a main indication for microsurgery with resulting pregnancy rates up to 84%. Salpingostomy and dense adhesiolysis have the lowest success rates (term pregnancy rates: 3-65%). Proximal tubal obstructions can be successfully treated by tubocornual anastomosis. Hydrosalpinges should be removed prior to in-vitro fertilization if they cannot be reconstructed. ART is recommended for patients older than 37-38 years, for women with severe tubal pathology, after repeated ectopic pregnancies, and in case of male infertility. SUMMARY: Tubal reconstructive surgery still plays a role in infertility treatment. ART has not replaced microsurgery routinely as first-line treatment for tubal infertility.