Cordula Schippert

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

BackgroundPreeclampsia (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.MethodsA 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.ResultsA 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.ConclusionAlthough 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.

RETRACTED: Reconstructive, organ-preserving microsurgery in tubal infertility: still an alternative to in vitro fertilization

In this retrospective study, we observed a total of 553 patients with tubal infertility who underwent microsurgical reconstructive surgery of the fallopian tubes (including adhesiolysis, anastomosis, fimbrioplasty, salpingostomy, and refertilization after former sterilization). The pregnancy (43.4%) and birth (29.2%) rates after microsurgery for acquired tubal damages (abortion: 6.4%; ectopic pregnancy: 7.9%) were higher than after single in vitro fertilization (28.4% and <20%, respectively; data from German IVF register). The pregnancy (73%) and birth (50.6%) rates after the reversal of sterilization also were higher (abortion: 15.7%; ectopic pregnancy: 6.7%). The advantages of reconstructive microsurgery over in vitro fertilization include the ideally permanent restoration of a womans ability to conceive naturally in every cycle that she ovulates, a high postoperative birth rate overall, and avoidance of multiple births.

Aromatase Inhibitors as Solely Treatment in Postmenopausal Breast Cancer Patients

Abstract:  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 cost efficiency of HPV vaccines is significantly underestimated due to omission of conisation-associated prematurity with neonatal mortality and morbidity

Introduction: Cervical intraepithelial neoplasia (CIN) represents the precursor of invasive cervical cancer and is associated with human papillomavirus infection (HPV) against which two vaccines have been approved in the last years. Standard treatments of high-grade CIN are conisation procedures, which are associated with an increased risk of subsequent pregnancy complications like premature delivery and possible subsequent life-long disability. HPV vaccination has therefore the potential to decrease neonatal morbidity and mortality. This has not been taken into account in published cost-effectiveness models. Material and Methods: We calculated the possible reduction rate of conisations for different vaccination strategies for Germany. Using this rate, we computed the reduction of conisation-associated preterm deliveries, life-long disability and neonatal death due to prematurity. The number of life-years saved (LYS) and gain in quality-adjusted life-years (QALYs) was estimated. The incremental costs per LYS / additional QALY were calculated. Results: The reduction of conisation procedures was highest in scenario I (vaccination coverage 90% prior to HPV exposition) with about 50%. The costs per LYS or additional QALY were lowest in scenario I, II and III with 45,101 € or 43,505–47,855 € and rose up to 60,544 € or 58,401–64,240 € in scenario V (50% vaccinated prior to sexual activity + additional 20% catch-up at a mean age of 20 y). Conclusion: Regarding the HPV 16 / 18 vaccines as “vaccines against conisation-related neonatal morbidity and mortality” alone, they already have the potential to be cost-effective. This effect adds up to reduction of cervical cancer cases and decreased costs of screening for CIN. Further studies on cost-effectiveness of HPV vaccination should take the significant amount of neonatal morbidity and mortality into account.

Mutations in WNT9B are associated with Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer–Rokitansky–Küster–Hauser syndrome (MRKHS) is a well‐known malformation pattern of the Müllerian ducts (MDs) characterized by congenital absence of the uterus and vagina. To date, most cases remain unexplained at molecular level. As female Wnt9b‐/‐ mice show a MRKHS‐like phenotype, WNT9B has emerged as a promising candidate gene for this disease. We performed retrospective sequence analyses of WNT9B in 226 female patients with disorders of the MDs, including 109 patients with MRKHS, as well as in 135 controls. One nonsense mutation and five likely pathogenic missense mutations were detected in WNT9B. Five of these mutations were found in cases with MRKHS accounting for 4.6% of the patients with this phenotype. No pathogenic mutations were detected in the control group (p = 0.017). Interestingly, all of the MRKHS patients with a WNT9B mutation were classified as MRKHS type 1, representing 8.5% of the cases from this subgroup. In previous studies, two of the patients with a WNT9B mutation were found to carry either an additional deletion of LHX1 or a missense mutation in TBX6. We conclude that mutations in WNT9B were frequently associated with MRKHS in our cohort and some cases may be explained by a digenic disease model.

Organ-preserving and reconstructive microsurgery of the fallopian tubes in tubal infertility: still an alternative to in vitro fertilization (IVF).

Tubal infertility mostly results from infections. Conception only is possible through complex treatments (in vitro fertilization or surgery). Success cannot be guaranteed, even after repeated treatments. Unfortunately, many couples are not informed about the prospect for success of tubal reconstruction. Problems of in vitro fertilization are low pregnancy and birth rates of 28.4% and <20% respectively (Germany) and the high number of multiple pregnancies (21%). In this retrospective study 462 women with acquired tubal infertility and further 127 women after previous sterilization underwent microsurgical treatment (microsurgical adhesiolysis, anastomosis, fimbrioplasty, salpingostomy, and refertilization due to former sterilization). The main outcome measures are the pregnancy and birth rates following the microsurgical procedure. Pregnancy and birth rates of 43.4% and 29.2%, respectively, were higher than the outcomes post-single in vitro fertilization (abortion: 6.4%, extrauterine pregnancy: 7.9%). When reversal of sterilization was performed, pregnancy and birth rates were higher at 73% and 50.6%, respectively (abortion: 15.7%, extrauterine pregnancy: 6.7%). The advantages of reconstructive microsurgery over in vitro fertilization include the ideally permanent restoration of womans ability to conceive naturally (repeated pregnancies are possible without further therapy), a high postoperative birth rate overall, and avoidance of multiple births. It is advisable to inform the patient about the objective possibility of reconstructive tubal surgery.

Awareness, knowledge, and perceptions of infertility, fertility assessment, and assisted reproductive technologies in the era of oocyte freezing among female and male university students

PurposeThe aims of our study were to analyze university student’s knowledge and attitude towards parenthood, female fertility, fertility assessment, and oocyte freezing and to explore associations between these aspects and the participant’s sex or degree program they were registered for.MethodsThe study was designed as an online-based cross-sectional survey. A total of 1144 participants answered 27 questions. The data were analyzed using descriptive statistics. Linear regression models were employed to explore associations between sex or university program and attitude towards parenthood, fertility assessment, and oocyte freezing.ResultsFemale students and students of non-medical degree programs were more likely to plan to have children earlier than male students or students of medical degree programs. Female sex or medical degree program was associated with an overall better knowledge about women’s fertility. The better the participant’s knowledge about fertility, the more likely the students would consider assisted reproductive technology (ART) treatments as an option to become pregnant when ovarian reserve is low. The majority of students knew the principal of oocyte freezing but would not consider using it. However, in the case of a low ovarian reserve, oocyte freezing would be accepted as an option.ConclusionsStudents planned to have children at an age when women’s fertility is already declining. Gaps in knowledge about female fertility and the potential of ART were more pronounced in male students and students of non-medical degree programs suggesting an increase of fertility awareness is necessary in these groups to prevent them from infertility and unwanted childlessness.

Lack of Associations between Female Hormone Levels and Visuospatial Working Memory, Divided Attention and Cognitive Bias across Two Consecutive Menstrual Cycles

Background: Interpretation of observational studies on associations between prefrontal cognitive functioning and hormone levels across the female menstrual cycle is complicated due to small sample sizes and poor replicability. Methods: This observational multisite study comprised data of n = 88 menstruating women from Hannover, Germany, and Zurich, Switzerland, assessed during a first cycle and n = 68 re-assessed during a second cycle to rule out practice effects and false-positive chance findings. We assessed visuospatial working memory, attention, cognitive bias and hormone levels at four consecutive time-points across both cycles. In addition to inter-individual differences we examined intra-individual change over time (i.e., within-subject effects). Results: Estrogen, progesterone and testosterone did not relate to inter-individual differences in cognitive functioning. There was a significant negative association between intra-individual change in progesterone and change in working memory from pre-ovulatory to mid-luteal phase during the first cycle, but that association did not replicate in the second cycle. Intra-individual change in testosterone related negatively to change in cognitive bias from menstrual to pre-ovulatory as well as from pre-ovulatory to mid-luteal phase in the first cycle, but these associations did not replicate in the second cycle. Conclusions: There is no consistent association between womens hormone levels, in particular estrogen and progesterone, and attention, working memory and cognitive bias. That is, anecdotal findings observed during the first cycle did not replicate in the second cycle, suggesting that these are false-positives attributable to random variation and systematic biases such as practice effects. Due to methodological limitations, positive findings in the published literature must be interpreted with reservation.

Treatment of high grade cervical intraepithelial neoplasia by photodynamic therapy using hexylaminolevulinate may be costeffective compared to conisation procedures due to decreased pregnancy-related morbidity.

Standard treatments of high‐grade Cervical intraepithelial neoplasia (CIN) are conisation procedures. Theses methods have proven effectiveness but are associated with an increased risk of subsequent pregnancy complications. Recently, photodynamic therapy (PDT) of CIN using hexylaminolevulinate (HAL) may represent an alternative treatment without the risk of cervical insufficiency or scaring. This study aims to evaluate the economical aspect of CIN treatment including associated pregnancy complications by comparing both methods.

A mixture model of nuchal translucency thickness in screening for chromosomal defects: validation of a single operator dataset.

(1) To validate the mixture model in a single operator dataset and (2) to compare the detection rates for fetal chromosomal defects obtained from the mixture model with those obtained from either the delta nuchal translucency (NT) or log multiple of the median (MoM) approach.