Pregnancies in women with antineutrophil cytoplasmatic antibody associated vasculitis.

PURPOSE OF REVIEW: Antineutrophil cytoplasmatic antibody associated vasculitis (AAV) usually manifests after age fifty, thus making it very rare during reproductive age. Although rare, AAV, particularly eosinophilic granulomatosis with polyangiitis, can manifest at a younger age. AAV can also appear for the first time during pregnancy. RECENT FINDINGS: Data from pregnant patients with AAV mostly derive from case reports or retrospective studies, with an absolute number of <100 published cases. Therefore, numbers of results of pregnancy outcome vary widely. SUMMARY: As with other chronic autoimmune diseases, patients and infants seem to be at a higher risk for preterm delivery, intrauterine growth retardation and preeclampsia. Possible treatment for AAV in pregnancy depends upon gestational age and include glucocorticosteroids, azathioprine, intravenous immunoglobulins, and in severe cases rituximab and even cyclophosphamide. Plasma exchange might be an option in selected patients. Aside from cyclophosphamide these medications can also be used during breastfeeding. Acetylsalicylic-acid 100-150 mg/day reduces the risk of preeclampsia, also in this population. Patients should be counseled prior to conception and medication that is suitable for pregnancy should be established early on. During pregnancy, we recommend close monitoring of disease activity, blood pressure and ideally to co-consult with a gynecologist in an interdisciplinary approach.

Optimal management of ANCA-associated vasculitis before and during pregnancy: current perspectives.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of systemic vasculitis characterized by autoantibodies against neutrophil cytoplasmic antigens (proteinase 3 PR3-ANCA and myeloperoxidase MPO-ANCA) and inflammation of small vessels. AAV include the diagnosis Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), which share many clinical and pathological features. Immunomodulatory therapies have significantly improved prognosis during the last decade. Nevertheless, especially in undiagnosed and thus uncontrolled AAV mortality due to renal impairment or pulmonary haemorrhages is still high. AAV are rare in fertile women, as the typical age of manifestation is above 50 years but there are women with AAV who are or want to become pregnant. This review focusses on how to manage patients with AAV planning to become pregnant and during their pregnancy.

Certification as dysplasia unit and its impact on large loop electrosurgical excision (LEEP).

PURPOSE: This study evaluates the overall treatment indicators and outcomes of patients who underwent loop electrosurgical excision procedure (LEEP) at the Department of Women's Health Tübingen and the impact of certification as a dysplasia unit on treatment quality. METHODS: Retrospective data analysis of 1596 patients from 2013 to 2018 who underwent LEEP excision at the Department of Women's Health Tübingen. Data of cytology, colposcopy, biopsy, LEEP histology, repeat LEEP histology and general characteristics were collected and analyzed descriptively. RESULTS: 85.4% (1364) of patients had CIN 2 + and 14.6% (232) had CIN 1 or normal findings on LEEP histology. The proportion of CIN 2 + excisions increased significantly from 82.4% in 2013 to 89% in 2018. The concordance of HSIL biopsy and LEEP histology was 89.1% in 2013 and 92.6% in 2018. In 2018, more biopsies and colposcopies were performed before excision. Complete resection (R0) was achieved in 88.3% of all excisions. R0 rates in patients with CIN 3 increased in 2014-2017 compared to 2013, resulting in fewer Re-LEEP excisions and hysterectomies. CONCLUSION: Certification as a dysplasia unit and the associated requirements have improved the diagnostic quality for patients with cervical dysplasia undergoing LEEP. This was demonstrated by several treatment indicators such as the number of colposcopies and biopsies and treatment outcomes such as an increased proportion of CIN 2 + excisions and R0 resections.

Uterine allograft removal by total laparoscopic hysterectomy after successful cesarean delivery in a living-donor uterus recipient with uterovaginal agenesis (MRKHS).

PURPOSE: To limit the burden of long-term immunosuppression (IS) after uterus transplantation (UTx), removal of the uterine allograft is indicated after maximum two pregnancies. Hitherto this has required graft hysterectomy by laparotomy. Our objective was to demonstrate, as a proof of concept, the feasibility of less traumatic transplantectomy by total laparoscopic hysterectomy (TLH). PATIENT: A 37-year-old woman with uterovaginal agenesis due to Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) who had undergone neovaginoplasty at age 19 years prior to living-donor (LD) UTx in 10/2019 at age 35 years gave birth to a healthy boy by primary cesarean section in 06/2021. During pregnancy, she developed impaired renal function, with bilateral hydronephrosis, necessitating early allograft removal in 09/2021 to prevent chronic kidney disease, particularly during a potential second pregnancy. METHODS: Transplantectomy by TLH essentially followed standard TLH procedures. We paid meticulous attention to removing as much donor tissue as possible to prevent postoperative complications from residual donor tissue after stopping IS, as well as long-term vascular damage. RESULTS: TLH was performed successfully without the need to convert to open surgery. Surgical time was 90 min with minimal blood loss. No major complications occurred intra- or postoperatively and during the subsequent 9-month follow-up period. Kidney function normalized. CONCLUSIONS: To our knowledge, we report the first successful TLH-based removal of a uterine allograft in a primipara after LD UTx, thus demonstrating the feasibility of TLH in uterus recipients with MRKHS.

Association of levonorgestrel intrauterine devices with stress reactivity, mental health, quality of life and sexual functioning: A systematic review.

Levonorgestrel-intrauterine-devices (LNG-IUD) are one of the most used contraceptive methods worldwide. While several reviews exist on how LNG-IUDs impact physiology and gynaecological functions, this systematic review focuses on stress, mental health, quality of life, sexual functioning, and effects on brain architecture. While data on stress is scarce, results on mental health are ambiguous. More consistently, LNG-IUD use seems to improve quality of life and sexual functioning. No studies highlighting the consequences of LNG-IUD use on the brain were found. The reviewed studies are characterized by a substantial variation in approaches, participant groups, and study quality. More high-quality research assessing the effects of LNG-IUD on mental health, including response to stressors and brain function and structure, is needed to identify women vulnerable to adverse effects of LNG-IUD, also in comparison to oral contraceptives, and to empower women to make more informed choices concerning hormonal contraception.

Sexual dysfunction and depression in Behçet's disease in comparison to healthy controls.

Behçet's disease (BD) can affect the genital system and is more common in Middle Eastern countries and Asia but also occurs in Caucasian people. Aim of this study was to evaluate the prevalence of sexual dysfunction (SD) and depression in patients with BD compared to a healthy control group (HCG). In addition, differences with regard to depression and patients' origin were evaluated. This prospective, monocentric study included 106 consecutive patients from our specialized BD outpatient clinic. Patients were asked to fill out the paper based standardized and validated questionnaires International Index of Erectile Function (IIEF), the Female Sexual Function Index (FSFI) and the Beck Depression Inventory (BDI). In addition, 206 healthy controls were asked to fill out the questionnaires. 106 patients with BD were evaluated and 206 participants in the HCG. The mean age in BD group was 40.5 years as compared to 44.4 years in the HCG. Half of the patients had Middle Eastern and half Caucasian origin. SD was found in 24.5% of all subjects. Only 6.9% of male patients showed signs of SD, while half of the women's group was suffering from SD. The prevalence for SD was significantly higher in women with Middle Eastern ethnic origin compared to women with Caucasian origin (75 vs. 33.3%, p = 0.024). Erectile Dysfunction occurred in 55% of all male patients which was not statistical different from the HCG. Genital ulcers affected 73.6% of all patients. Depression was found in 36.7% of all subjects as compared to 6.25% in the HCG (p < 0.001). Both, SD and depression correlated positively in males (p = 0.017) and females (p = 0.013). SD and depression are very common problems in BD and should be addressed by the treating physician. Both manifestations are intensifying each other. Depression especially is more prevalent compared to the healthy population.

Opinion paper: gynecological surgery in local anesthesia?

PURPUSE: The paracervical block (PCB) is a local anesthesia procedure that can be used to perform gynecological surgeries without the need for further anesthesia. With the PCB, surgeries can be moved from the central operating room to outpatient operating rooms, where they can be performed without the presence of an anesthesia team. METHODS: In this paper, the indications, implementation and limitations of the procedure are discussed. CONCLUSION: Especially in times of scarce staff and OR resources during the Corona pandemic, OR capacity can be expanded in this way.

Characterization and clinical management of abnormal cytology findings in pregnant women: a retrospective analysis.

PURPOSE: The diagnosis of cervical intraepithelial neoplasia during pregnancy poses a great challenge to the treating clinician and the patient. According to the current guidelines, watchful waiting during pregnancy can be justified. Only in cases of invasion, immediate treatment may be indicated. However, few data are available on the management of cervical dysplasia during pregnancy. Further research is important for counselling affected women. METHODS: Data of pregnant patients with suspected cervical dysplasia who presented to the University Women's Hospital Tübingen between 2008 and 2018 were evaluated retrospectively. Colposcopic, cytologic, and histologic assessment was performed for diagnosis. Data on remission, persistence and progression of disease based on histologic and cytologic assessment and the mode of delivery were correlated. RESULTS: 142 patients were enrolled. Cytology at first presentation was PAPIII (-p/-g) in 7.0%, PAPIIID (IIID1/IIID2) in 38.7%, PAPIVa (-p/-g) in 50.0%, PAPIVb (-p) in 2.8%, and PAPV (-p) in 1.4%. All cases with suspected invasion were recorded at the initial presentation. Complete histological or cytological remission was observed in 24.4%, partial remission in 10.4%, persistence in 56.3%, and progression in 8.9%. In two cases (1.5%) progression to squamous cell carcinoma occurred. CONCLUSIONS: Watchful waiting for cervical intraepithelial neoplasia during pregnancy seems to be sufficient and oncologically safe. It is important to exclude invasion during pregnancy, to perform frequent colposcopic, cytologic and histologic examinations and to ensure a postpartum follow-up examination to initiate the treatment of high-grade lesions. Spontaneous delivery seems to be safe in patients with cervical dysplasia, Caesarean section is not indicated.

Sexual function in German women with systemic sclerosis compared to women with systemic lupus erythematosus and evaluation of a screening test.

OBJECTIVES: To assess and compare sexual dysfunction (SDF) in female patients with systemic sclerosis (SSc) or systemic lupus erythematosus (SLE), to correlate sexual function with disease characteristics and depression, and to evaluate a short questionnaire (Qualisex) as a screening test. METHODS: Female patients with systemic sclerosis or systemic lupus erythematosus in two German tertiary university hospitals were evaluated in a prospective study. A self-designed questionnaire, the Female Sexual Function Index (FSFI), the Qualisex, and the Beck's depression inventory were used. RESULTS: 171 female patients were included into the study (83 with SSc, and 88 with SLE). 62.6% (52 of 83) of SSc patients and 67.0% (59 of 88) of SLE patients were sexually active. Only 9.6% of SSc patients and 14.8% of SLE patients had ever discussed sexual problems with their physician. Significantly more SSc patients would wish to discuss sexuality with their physician more intensively (37.3% vs. 28.4% in SLE patients, p=0.011). Among the 51 sexually active and evaluable SSc patients a mean FSFI of 25.53 (±5.06) was found, with a FSFI value defining sexual dysfunction (SDF) (<26.55) in 49% of patients, which did not differ significantly compared to SLE patients (n=59, mean FSFI 26.92 (±5.17), SDF in 45.8%). The Qualisex correlated significantly with the FSFI, and both Qualisex and FSFI correlated with depressiveness. CONCLUSIONS: Sexual dysfunction (SDF) is a frequent problem in female patients with SSc and SLE. Addressing sexual issues during medical consultation is an unmet need. The Qualisex constitutes a short questionnaire, which is suitable for addressing concerns on sexuality.

Prevalence of autoimmune disease in women with premature ovarian failure.

Objective: The aim of the study was to investigate the relationship between premature ovarian failure and autoimmune disease.Methods: This interdisciplinary prospective study included 52 consecutively recruited women with premature ovarian failure, aged 18-40 years. Diagnosis of premature ovarian failure was defined as amenorrhoea lasting more than 4 months and anti-Müllerian hormone levels below the age-appropriate range. Women with an abnormal karyotype or Fragile X syndrome were excluded from the study. All participants were screened by a rheumatologist for the presence of underlying autoimmune disease.Results: The average age at first diagnosis of premature ovarian failure was 29.5 years; 92.3% of participants (n = 48) presented with a secondary amenorrhoea, while only 7.7% (n = 4) had primary amenorrhoea. Of all 52 participants, 40.4% (n = 21) had at least one confirmed autoimmune disease, including Hashimoto's disease, systemic lupus erythematosus, rheumatoid arthritis, psoriasis, Crohn's disease, polyglandular autoimmune syndrome and coeliac disease. Response rates for hormonal stimulation therapy were low and the presence of autoimmune disease was associated with poor infertility treatment outcome.Conclusions: We found a high prevalence of autoimmune disease in women with premature ovarian failure. Screening for autoimmune diseases should be offered to all women with premature ovarian failure.

Longitudinal Clinical Performance of the RNA-Based Aptima Human Papillomavirus (AHPV) Assay in Comparison to the DNA-Based Hybrid Capture 2 HPV Test in Two Consecutive Screening Rounds with a 6-Year Interval in Germany.

Longitudinal data on the E6/E7 mRNA-based Aptima human papillomavirus (AHPV) assay exceeding three years in comparison to the gold standard Digene Hybrid Capture 2 (HC2) test are not available. We previously reported the cross-sectional data of the German AHPV Screening Trial (GAST) in which 10,040 women were recruited and tested by liquid-based cytology, the HC2 assay, and the AHPV assay. Four hundred eleven test-positive women were followed for up to six years. In addition, 3,295 triple-negative women were screened after a median time of six years. Overall, 28 high-grade cervical intraepithelial neoplasia (CIN3) cases were detected. The absolute risk of developing high-risk HPV-positive CIN3+ over six years among those women that tested negative at baseline was 2.2 (95% confidence interval [95% CI], 1.0 to 4.9) and 3.1 (95% CI, 1.7 to 5.7) per 1,000 women screened by the HC2 and the AHPV tests; the additional risk for those with AHPV-negative compared with HC2-negative results was 0.9 (95% CI, -0.2 to 2.1) per 1,000. In comparison, the absolute risk following a negative LBC test was 9.3 (95% CI, 2.9 to 30.2). The relative sensitivity of AHPV compared to HC2 was 91.5% for CIN3+, and the negative predictive values were 99.8% (95% CI, 99.5 to 99.9%) for HC2 and 99.7% (95% CI, 99.4 to 99.8%) for AHPV. Our data show that the longitudinal performance of the AHPV test over six years is comparable to the performance of the HC2 test and that the absolute risk of CIN3+ over six years following a negative AHPV result in a screening population is low. (This study is registered at ClinicalTrials.gov under registration number NCT02634190.).

Fertility protection: complications of surgery and results of removal and transplantation of ovarian tissue.

Fertility-preserving measures are becoming important for patients receiving oncological treatment. One method involves cryopreservation of ovarian tissue and transplanting it when treatment is completed. We report complications resulting from surgical and fertility medicine, and the results of procedures for the removal and transplantation of ovarian tissue carried out within the FertiProtekt network. A survey using a structured questionnaire was conducted among the FertiProtekt network centres between November 2015 and June 2016. The analysis included surgical techniques used to remove and transplant ovarian tissue, surgical complications and results. Laparoscopic removal and transplantation of ovarian tissue have a low risk of complications. Surgical complications occurred in three of the network's 1373 ovarian tissue removals (n = 1302) and transplantations (n = 71); two complications (0.2%) occurred during removal and one during transplantation. Menstruation resumed in 47 out of 58 women (81%) who underwent ovarian tissue transplantation. Hormonal activity occurred in 63.2% of transplantations with a follow-up of 6 months or over. Sixteen pregnancies occurred in 14 patients, with nine births. The risks and complications of removal and transplantation of ovarian tissue are similar to those of standard laparoscopy. These procedures are becoming standard for fertility protection in cancer patients.

Hyperandrogenemia and ovarian reserve in patients with Mayer-Rokitansky-Küster-Hauser syndrome type 1 and 2: potential influences on ovarian stimulation.

PURPOSE: This study aimed to analyze the hormone profiles, to detect the rate of hyperandrogenemia and to investigate the potential effect of Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) on ovarian reserve, as reflected by the serum Anti-Mullerian hormone (AMH) levels. Clinical implications were analyzed by including our own experiences with three patients after ovarian stimulation in preparation for uterus transplantation. METHODS: Serum samples of 100 patients with MRKHS (50 patients with MRKHS type 1 and 50 with type 2) were analyzed and compared to 50 individually age-matched healthy controls. Blood samples for hormone analyses were collected routinely during the clinical visit. RESULTS: The mean age was 20.0 years for MRKHS type 1, MRKHS type 2 and healthy controls. Compared to healthy controls, there was no significant difference in AMH values in the MRKH patients. As shown in previous studies, the proportion of hyperandrogenemia without clinical symptoms was significantly higher in MRKHS type 1 (52%; p < 0.001) and type 2 (56%; p < 0.001) patients when compared to age-matched controls. In preparation for uterus transplantation, three patients were stimulated with FSH/hMG for mean 14.2 days and the mean number of aspirated oocytes was 13.2 (3-22), while 8.3 (2-10) oocytes could be fertilized and cryopreserved. The mean fertilization rate was 51.2% (30-67%). CONCLUSION: The rate of hyperandrogenemia was significantly higher in MRKH patients compared to healthy age-matched controls. Though, ovarian reserve (AMH level) was not reduced compared to controls. Future studies are needed to identify optimal ovarian stimulation protocols as well as to implement a systematic multicenter reporting system.

Selecting living donors for uterus transplantation: lessons learned from two transplantations resulting in menstrual functionality and another attempt, aborted after organ retrieval.

PURPOSE: To contribute to establishing donor selection criteria based on our experience with two successful living-donor human uterus transplantations (UTx) and an aborted attempt. METHODS: This interventional study included three patients with uterine agenesis, aged 23, 34, and 23 years, scheduled for UTx, and their uterus-donating mothers, aged 46, 61, and 46 years, respectively. Interventions included preoperative investigations, donor surgery, back-table preparation, and recipient surgery. Preoperative imaging, surgical data, histopathology, menstrual pattern, and uterine blood flow were the main outcome measures. RESULTS: In the first case (46-year-old mother/23-year-old daughter), donor/recipient surgery took 12.12/5.95 h. Regular spontaneous menstruations started 6-week post-transplantation, continuing at 24-28-day intervals throughout the 6-month observation period. Repeated follow-up cervical biopsies showed no signs of rejection. In the second case (61-year-old donor), surgery lasted 13.10 h; attempts to flush the retrieved uterus failed due to extreme resistance of the left uterine artery (UA) and inability to perfuse the right UA. Transplantation was aborted to avoid graft vessel thrombosis or insufficient blood flow during potential pregnancy. Histopathology revealed intimal fibrosis and initial sclerosis (right UA), extensive intimal fibrosis (parametric arterial segments), and subtotal arterial stenosis (myometrial vascular network). In the third case (46-year-old mother/23-year-old daughter), donor/recipient surgery took 9.05/4.52 h. Menstruations started 6-week post-transplantation. Repeated cervical biopsies showed no signs of rejection during the initial 12-week follow-up period. CONCLUSIONS: Meticulous preoperative evaluation of potential living uterus donors is essential. This may include selective contrast-enhanced UA angiograms and limitation of donor age, at least in donors with risk factors for atherosclerosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03048396.

Decidualization is Impaired in Endometrial Stromal Cells from Uterine Rudiments in Mayer-Rokitansky-Küster-Hauser Syndrome.

BACKGROUND/AIMS: Uterine rudiments from patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) contain all tissues typically found in the uterus. Endometrium from the rudiments predominantly exhibits basalis-like features, and endometrial proliferative capacity in patients' epithelium and stroma is significantly lower. METHODS: This single-center, prospective study conducted at a major German university hospital compared in-vitro decidualization in cultured ESCs from MRKHS patients and hysterectomy controls. Primary ESC cultures were established from both sources. Hormone-induced prolactin and IGFBP-1 secretion served as a measure of their ability to undergo decidualization in response to hormonal stimulation. Expression levels of 8 key marker genes of decidualization were also determined. RESULTS: At day 9, mean secretion of prolactin and IGFBP-1 was significantly reduced by 89.0% and 99.5%, respectively, in MRKHS ESCs vs. hysterectomy controls, both indicating impaired decidualization of MRKHS ESCs. Key decidual markers confirmed impaired decidualization in MRKHS patients. CONCLUSION: Our results indicate that the ESCs from MRKHS patients lack hormone responsiveness as a potential sign of dysfunctional hormone receptor function, which may also play a role in the onset of MRKHS. Further studies are needed to corroborate our findings, directly address receptor function, and elucidate the role of other potential determinants of uterine development and adult function.

Sequence variants in ESR1 and OXTR are associated with Mayer-Rokitansky-Küster-Hauser syndrome.

INTRODUCTION: Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterized by congenital absence of the uterus and the upper two-thirds of the vagina in otherwise phenotypically normal females. It is found isolated or associated with renal, skeletal and other malformations. Despite ongoing research, the etiology is mainly unknown. For a long time, the hypothesis of deficient hormone receptors as the cause for MRKHS has existed, supported by previous findings of our group. The aim of the present study was to identify unknown genetic causes for MRKHS and to compare them with data banks including a review of the literature. MATERIAL AND METHODS: DNA sequence analysis of the oxytocin receptor (OXTR) and estrogen receptor-1 gene (ESR1) was performed in a group of 93 clinically well-defined patients with uterovaginal aplasia (68 with the isolated form and 25 with associated malformations). RESULTS: In total, we detected three OXTR variants in 18 MRKHS patients with one leading to a missense mutation, and six ESR1 variants in 21 MRKHS patients, two of these causing amino acid changes and therefore potentially disease. CONCLUSIONS: The identified variants on DNA level might impair receptor function through different molecular mechanisms. Mutations of ESR1 and OXTR are associated with MRKHS. Thus, we consider these genes potential candidates associated with the manifestation of MRKHS.

Evaluation of the HystSim™-virtual reality trainer: an essential additional tool to train hysteroscopic skills outside the operation theater.

BACKGROUND: Minimally invasive surgery is a major pillar of gynecological surgery. However, there are very few training opportunities outside the operation theater (OR) due to the cost and equipment requirements of organ simulators, virtual reality trainers (VRT) are promising tools to fill this gap. METHODS: Experienced and inexperienced participants of a minimally invasive surgery course followed the standardized HystSim™-VRT training program. RESULTS: Performance of 39 Participants (15 inexperienced and 24 experienced) was evaluated in the standardized hysteroscopic program HystSim™. Tasks included three rounds of both a polyp and a myoma resection. Primary measurements were improvement in resection time, cumulative resection path length, and distention media use. CONCLUSION: The HystSim™-VRT is an effective tool to improve the psychomotor skills needed in hysteroscopic surgery for experienced and inexperienced surgeons prior to OR exposure. Additional organ models training is advisable for hysteroscopic haptic skills.

Low-molecular-weight heparin for women with unexplained recurrent pregnancy loss: a multicenter trial with a minimization randomization scheme.

BACKGROUND: A daily injection of low-molecular-weight heparin (LMWH) is often prescribed to women with unexplained recurrent pregnancy loss (RPL), although evidence suggesting a benefit is questionable. OBJECTIVE: To determine whether LMWH increases ongoing pregnancy and live-birth rates in women with unexplained RPL. DESIGN: Controlled, multicenter trial with randomization using minimization conducted from 2006 to 2013. (ClinicalTrials.gov: NCT00400387). SETTING: 14 university hospitals and perinatal care centers in Germany and Austria. PATIENTS: 449 women with at least 2 consecutive early miscarriages or 1 late miscarriage were included during 5 to 8 weeks' gestation after a viable pregnancy was confirmed by ultrasonography. INTERVENTION: Women in the control group received multivitamin pills, and the intervention group received vitamins and 5000 IU of dalteparin-sodium for up to 24 weeks' gestation. MEASUREMENTS: Primary outcome was ongoing pregnancy at 24 weeks' gestation. Secondary outcomes included the live-birth rate and late pregnancy complications. RESULTS: At 24 weeks' gestation, 191 of 220 pregnancies (86.8%) and 188 of 214 pregnancies (87.9%) were intact in the intervention and control groups, respectively (absolute difference, -1.1 percentage points [95% CI, -7.4 to 5.3 percentage points]). The live-birth rates were 86.0% (185 of 215 women) and 86.7% (183 of 211 women) in the intervention and control groups, respectively (absolute difference, -0.7 percentage point [CI, -7.3 to 5.9 percentage points]). There were 3 intrauterine fetal deaths (1 woman had used LMWH); 9 cases of preeclampsia or the hemolysis, elevated liver enzyme level, and low platelet count (HELLP) syndrome (3 women had used LMWH); and 11 cases of intrauterine growth restriction or placental insufficiency (5 women had used LMWH). LIMITATION: Placebo injections were not used, and neither trial staff nor patients were blinded. CONCLUSION: Daily LMWH injections do not increase ongoing pregnancy or live-birth rates in women with unexplained RPL. Given the burden of the injections, they are not recommended for preventing miscarriage. PRIMARY FUNDING SOURCE: Pfizer Pharma.

Granulocytic myeloid derived suppressor cells expand in human pregnancy and modulate T-cell responses.

Immune tolerance toward the semiallogeneic fetus plays a crucial role in the maintenance of pregnancy. Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterized by their ability to modulate T-cell responses. Recently, we showed that MDSCs accumulate in cord blood of healthy newborns, yet their role in materno-fetal tolerance remained elusive. In the present study, we demonstrate that MDSCs with a granulocytic phenotype (GR-MDSCs) are highly increased in the peripheral blood of healthy pregnant women during all stages of pregnancy compared with nonpregnant controls, whereas numbers of monocytic MDSCs were unchanged. GR-MDSCs expressed the effector enzymes arginase-I and iNOS, produced high amounts of ROS and efficiently suppressed T-cell proliferation. After parturition, GR-MDSCs decreased within a few days. In combination, our results show that GR-MDSCs expand in normal human pregnancy and may indicate a role for MDSCs in materno-fetal tolerance.

Head-to-Head Comparison of the RNA-Based Aptima Human Papillomavirus (HPV) Assay and the DNA-Based Hybrid Capture 2 HPV Test in a Routine Screening Population of Women Aged 30 to 60 Years in Germany.

Testing for E6/E7 mRNA in cells infected with high-risk (HR) human papillomavirus (HPV) might improve the specificity of HPV testing for the identification of cervical precancerous lesions. Here we compared the RNA-based Aptima HPV (AHPV) assay (Hologic) and the DNA-based Hybrid Capture 2 (HC2) HPV test (Qiagen) to liquid-based cytology (LBC) for women undergoing routine cervical screening. A total of 10,040 women, 30 to 60 years of age, were invited to participate in the study, 9,451 of whom were included in the analysis. Specimens were tested centrally by LBC, the AHPV test, and the HC2 test, and women who tested positive on any test were referred for colposcopy. Genotyping was performed on all HR-HPV-positive samples. Test characteristics were calculated based on histological review. As a result, we identified 90 women with cervical intraepithelial neoplasia grade 2+ (CIN2+), including 43 women with CIN3+. Sensitivity differences between the AHPV test and the HC2 test in detecting CIN2+ (P = 0.180) or CIN3+ (P = 0.0625) lesions were statistically nonsignificant. Of three CIN3 cases that were missed with the AHPV test, two cases presented lesion-free cones and one had a non-HR HPV67 infection. The specificity (