Gonadotropin Stimulation Reduces the Implantation and Live Birth Rate but Not the Miscarriage Rate of Embryos Transferred When Compared to Unstimulated In Vitro Fertilization.

Research suggests that gonadotropin stimulation in in vitro fertilization (IVF) treatment affects embryo quality and the endometrium that might influence embryo implantation, placentation and establishment of a viable pregnancy. We assessed the impact of gonadotropin stimulation on implantation, live birth and miscarriage rates per transferred embryo by comparing stimulated and unstimulated IVF treatment. In a cohort of 728 couples, 1310 IVF cycles with successful embryo transfer were analysed; 857 cycles were stimulated with gonadotropins > 75 IU/day (333 poor responder < 4 oocytes; 524 normal responders), and 453 were unstimulated. In total, 1913 fresh cleavage-stage embryos were transferred. Zygote but no embryo selection was performed, and supernumerous zygotes were vitrified. The implantation rate was defined as number of sonographically detected amniotic sacs; live birth rate as number of children born per transferred embryo. Modified mixed effect Poisson regression was used to account for the dependency of cycles and embryos within the same women and the same transfer cycle. Adjustments were made for maternal age, parity, primary or secondary infertility and indication for IVF. Per transferred embryo, implantation rates (rate ratio (RR) 1.37; 95% CI 1.04-1.81; p = 0.028; aRR 1.42; 95% CI 1.10-1.84; p = 0.008) and live birth rates (RR 1.33; 95% CI 0.95-1.86; p = 0.093; aRR 1.38; 95% CI 1.01-1.88; p = 0.044) were higher in NC-IVF compared to cIVF normal responders. Miscarriage did not differ (RR 0.99; 95% CI 0.59-1.65; p = 0.965; aRR 0.90; 95% CI 0.52-1.53 p = 0.698). Similar results were obtained in poor responders. The study suggests an impact of gonadotropin stimulation on the implantation potential of embryos

Supplementary dydrogesterone is beneficial as luteal phase support in artificial frozen-thawed embryo transfer cycles compared to micronized progesterone alone.

INTRODUCTION The number of frozen embryo transfers increased substantially in recent years. To increase the chances of implantation, endometrial receptivity and embryo competency must be synchronized. Maturation of the endometrium is facilitated by sequential administration of estrogens, followed by administration of progesterone prior to embryo transfer. The use of progesterone is crucial for pregnancy outcomes. This study compares the reproductive outcomes and tolerability of five different regimens of hormonal luteal phase support in artificial frozen embryo transfer cycles, with the objective of determining the best progesterone luteal phase support in this context. DESIGN This is a single-center retrospective cohort study of all women undergoing frozen embryo transfers between 2013 and 2019. After sufficient endometrial thickness was achieved by estradiol, luteal phase support was initiated. The following five different progesterone applications were compared: 1) oral dydrogesterone (30 mg/day), 2) vaginal micronized progesterone gel (90 mg/day), 3) dydrogesterone (20 mg/day) plus micronized progesterone gel (90 mg/day) (dydrogesterone + micronized progesterone gel), 4) micronized progesterone capsules (600 mg/day), and (5) subcutaneous injection of progesterone 25 mg/day (subcutan-P4). The vaginal micronized progesterone gel application served as the reference group. Ultrasound was performed after 12-15 days of oral estrogen (≥4 mg/day) administration. If the endometrial thickness was ≥7 mm, luteal phase support was started, up to six days before frozen embryo transfer, depending on the development of the frozen embryo. The primary outcome was the clinical pregnancy rate. Secondary outcomes included live birth rate, ongoing pregnancy, and miscarriage and biochemical pregnancy rate. RESULTS In total, 391 cycles were included in the study (median age of study participants 35 years; IQR 32-38 years, range 26-46 years). The proportions of blastocysts and single transferred embryos were lower in the micronized progesterone gel group. Differences among the five groups in other baseline characteristics were not significant. Multiple logistic regression analysis, adjusting for pre-defined covariates, showed that the clinical pregnancy rates were higher in the oral dydrogesterone only group (OR = 2.87, 95% CI 1.38-6.00, p=0.005) and in the dydrogesterone + micronized progesterone gel group (OR = 5.19, 95% CI 1.76-15.36, p = 0.003) compared to micronized progesterone gel alone. The live birth rate was higher in the oral dydrogesterone-only group (OR = 2.58; 95% CI 1.11-6.00; p=0.028) and showed no difference in the smaller dydrogesterone + micronized progesterone gel group (OR = 2.49; 95% CI 0.74-8.38; p=0.14) compared with the reference group. CONCLUSION The application of dydrogesterone in addition to micronized progesterone gel was associated with higher clinical pregnancy rate and live birth rate and then the use of micronized progesterone gel alone. DYD should be evaluated as a promising LPS option in FET Cycles

Living with endometriosis: Comorbid pain disorders, characteristics of pain and relevance for daily life

BACKGROUND: Pain plays a central role in endometriosis. The complex relationship among pain characteristics, comorbid pain disorders and daily life represents a challenge for medical support. This multicentre cross‐sectional case–control study analysed the association between endometriosis‐related chronic pain and functions of daily life in 510 women with endometriosis, 265 (52%) who experienced chronic pain, either from endometriosis alone (N = 134, 26.3%) or in association with additional pain disorders (N = 131, 25.7%). METHODS: Self‐administered questionnaires from the Brief Pain Inventory and the Pain Disability Index were used to investigate associations between pain characteristics (frequency, duration, intensity) and daily life. Also, associations between different endometriosis characteristics (rASRM stage, presence of adhesions, localisation of lesions) and pain were evaluated. RESULTS: Chronic pain is negatively associated with almost all (12/14) aspects of daily life investigated, including standing, walking, sitting, defaecation, sleep, sports activities, family and domestic responsibilities, sexuality, social functioning, professional life, mood, and joy of life. Altogether, 33.7% of women with chronic pain reported moderate and 27.5% severe limitations. Comorbid pain disorders resulted in significantly more limitations. The length of pain episodes showed a particularly important influence, especially for family/domestic responsibilities (OR 22.94, p < 0.001), professional life (OR 16.56, p < 0.001) and social functioning (OR 41.03, p < 0.001). CONCLUSIONS: Our data confirm that despite treatment, about 50% of women experience pain. Pain was associated with at least moderate negative effects on almost all areas of daily life; additional pain comorbidities increased limitations. Improving pain management is essential for improving quality of life in women with endometriosis. SIGNIFICANCE: The study provides an accurate overview of the impact of endometriosis‐associated pain on daily life. This is important because pain plays a central role in women living with endometriosis, and despite modern therapies, many women continue to suffer from chronic pain. The detailed analysis of its impact with a comprehensive survey of all aspects of daily life in a very large study population is unique. We expect an improved understanding of consequences of pain to significantly advance medical support in these patients

Improved Mechanical Properties of Chemically Amplified, Positive Tone, Polynorbornene Dielectric

The mechanical properties of an aqueous developed, chemically amplified, polynorbornene-based permanent dielectric have been investigated. The previously reported hexafluoroisopropanol norbornene and tert-butyl ester norbornene copolymer has been modified via two routes to improve the mechanical properties of the polymer and enable thick-film deposition. First, a third monomer, butyl norbornene (ButylNB) was added to the polymer backbone. The inclusion of 24 mol% ButylNB lowered the elastic modulus from 2.64 to 2.35 GPa and raised the dielectric constant from 2.78 to 3.48. The second approach added a low molecular weight, plasticizing additive in the copolymer formulation. Many additives were immiscible with the resin or did not affect the mechanical properties. Trimethyololpropane ethoxylate (TMPEO) was found to be a miscible additive that improved mechanical properties and could participate in crosslinking the final dielectric material. TMPEO interacted with the PAG, lowering its decomposition temperature. An optimal formulation and processing scheme were determined. A formulation with 10 pphr TMPEO was measured to have a dielectric constant of 2.94, an elastic modulus of 1.95 GPa, a sensitivity at 365 nm of 175 mJ/cm 2 , and a contrast of 4. Photo-definable, permanent, low-k dielectrics are widely used in the fabrication of microelectronic devices and packages. 1-5 These dielectrics electrically isolate the interconnect and mechanically stabilize the structures for the life of the device. On integrated circuits, organic dielectrics can be used for interlayer isolation and/or the stress buffer layer on top of the device. Stress buffer layers protect the top surface of the chip and can mitigate mechanical failures that arise from a mismatch of the coefficient of thermal expansion between the chip and package during thermal cycling. In microelectronics packages, low-k dielectrics can be used in the buildup layers, electrically separating the electrical conductors. Low permittivity is critical for use in these applications, as it affects device performance, energy loss, and signal integrity. Photo-definability is an attractive property for permanent polymeric dielectrics. The ability to directly pattern the dielectric by photolithographic techniques mitigates the need for a separate photoresist and pattern transfer steps. This can lower the overall fabrication cost and reduce the number of individual process steps. 2 For stress buffer and redistribution applications, positive tone photo-definable dielectrics are more desirable than negative tone ones because the lithographic mask is mostly opaque mask and less prone to transfer particle defects. Also, holes and lines in positive tone materials exhibit sloped sidewalls (opening wider at the top) which is beneficial for void-free plating of the copper interconnects. Aqueous developability is another attractive property, as it mitigates the need for environmentally harmful organic solvent developers. Further, the dielectric should exhibit high sensitivity and contrast for high throughput and high quality feature patterning. Previously, a chemically amplified, positive tone, permanent polynorbornene (PNB) dielectric was reported. 6 This dielectric was composed of a copolymer of hexafluoroisopropanol norbornene (HFANB) and tert-butyl ester norbornene (TBENB). The chemical structure of this polymer is shown in The contrast was measured to be ≥14.2. These lithographic values are more than an order of magnitude better than those reported for other positive tone dielectrics. Though the chemically amplified PNB dielectric had excellent properties, the dielectric exhibited cracking when coated to thickness greater than ∼3 μm on silicon wafers. This result is due to a combination of phenomena. First, the coefficient of thermal expansion (CTE) of the polymer (39.5 ppm/K) is not well-matched to silicon (3 ppm/K). This mismatch produces thermal stresses in the film upon cooling after the baking and curing steps. It is noted that other PNB dielectrics with similar CTEs have been deposited crack-free on silicon wafers at much greater thicknesses. In this paper, two approaches to improving the mechanical toughness of the chemically amplified PNB dielectric were investigated. First, a terpolymer of HFANB, TBENB, and a third monomer, butyl norbornene (ButylNB) was synthesized. The structure of the terpolymer is shown i

Physical Activity in Women with Endometriosis: Less or More Compared with a Healthy Control?

BACKGROUND Endometriosis, i.e., endometrial-like tissue outside the uterus, is a chronic inflammatory condition affecting physical functioning. However, the specific levels of physical activity (PA) in the context of endometriosis and different disease symptoms remain unclear. METHODS This multi-center, cross-sectional study compared PA levels and influencing factors in endometriosis patients and non-endometriosis patients. Data were collected through questionnaires. Endometriosis was surgically confirmed. A statistical analysis was performed with appropriate tests. RESULTS The study included 460 women with endometriosis and 460 age-matched women without this condition. The two groups did not differ significantly in terms of age, education level, or stable partnership. Women with endometriosis exhibited lower PA levels, practicing fewer hours of sports weekly and climbing fewer stairs daily compared to the control group. These differences remained significant after controlling for confounding factors. Factors such as endometriosis, current dysmenorrhea, and depression were associated with decreased PA. CONCLUSIONS These findings suggest that women with endometriosis engage in less PA compared to those without this condition. These results highlight the need for interventions to promote increased PA in endometriosis patients and harness the associated health benefits. Further research is warranted to explore the underlying mechanisms and develop tailored exercise therapies for this population

Thin Endometrium Is Also Associated With Lower Clinical Pregnancy Rate in Unstimulated Menstrual Cycles: A Study Based on Natural Cycle IVF

Introduction: Does the endometrial thickness (EMT) at the time of follicle aspiration correlate with the pregnancy rate in unstimulated menstrual cycles?Materials and Methods: This is a retrospective, observational single center study.105 women with regular menstrual cycles undergoing their first NC-IVF cycle with an embryo transfer were analyzed. Clinical pregnancy and live birth rates were calculated and data were adjusted for women's age, cycle day of follicle aspiration and body mass index (BMI).Results: Age of participants was 35.0 y [32.0; 37.0]. Follicle aspiration was performed on day 14.0 [12.0; 15.0] of the cycle. Total clinical pregnancy rate was 24.8% and live birth rate 15.2% per transfer. Pregnancy rate in women with endometrial thickness ≤7 mm (n = 27) was 7.4 and 30.8% in women &gt;7 mm (n = 78) (OR 5.56, 1.22–25.36) (P = 0.03). Live birth rates were not significantly different. Quadratic regression analysis revealed lower pregnancy rates in women with thin (around &lt;8 mm) as well as with thick (around &gt;11 mm) endometria. P-value after crude quadratic analysis was 0.028 and after adjustment for age, day of aspiration and BMI was 0.039. Significance was not reached for live birth rates.Conclusion: Thin endometrium should also be considered as an independent negative prognostic factor for achieving pregnancy in women without ovarian stimulation

The greater incidence of small for gestational age newborns after gonadotropin-stimulated in vitro fertilization with a supra-physiological estradiol level on ovulation trigger day.

INTRODUCTION Reproductive scientists have postulated various risk factors for lower birthweight following conventional gonadotropin stimulated in vitro fertilization compared to spontaneously conceived children: parental factors (age, health, duration of subfertility, and smoking habits); ovarian stimulation; laboratory procedures; the number of oocytes retrieved; and the number of embryos transferred. Our aim was to investigate the impact of gonadotropin stimulation and serum estradiol level on the risk of a newborn's being small for gestational age. MATERIAL AND METHODS We conducted a cohort study (2010-2016) of singletons (n = 155) born either after conventional gonadotropin stimulated in vitro fertilization (using ≥150 IU/d human gonadotropin for stimulation) or after natural cycle in vitro fertilization without any stimulation. We analyzed perinatal outcomes using birthweight percentiles, as they adjust for gestational age and sex. RESULTS The proportion of small for gestational age was 11.8% following conventional gonadotropin stimulated in vitro fertilization, and 2.9% after natural-cycle in vitro fertilization (P = 0.058). The odds of small for gestational age were significantly higher with supra-physiological estradiol levels in maternal serum on ovulation trigger day (unadjusted odds ratio 4.58; 95% confidence interval 1.35 to 15.55; P = 0.015). It remained significant after adjusting for maternal height, age, and body mass index (adjusted odds ratio 3.83; 95% confidence interval 1.06 to 13.82; P = 0.041). CONCLUSIONS We found an associated risk of children being born small for gestational age after conventional gonadotropin stimulated in vitro fertilization compared to natural-cycle in vitro fertilization. This higher risk is significantly associated with supra-physiological estradiol levels. We propose a reduction in the dosage of gonadotropin to minimize the risk of small for gestational age and future health consequences. This article is protected by copyright. All rights reserved

Does endometriosis affect professional life? A matched case-control study in Switzerland, Germany and Austria.

OBJECTIVES Endometriosis is a gynaecological disease most commonly causing severe and chronic pelvic pain as well as an impaired quality of life. The aim of this study was to investigate if and how endometriosis affects choices regarding professional life as well as the quality of daily working life. DESIGN, SETTING AND PARTICIPANTS In the context of a multicentre case-control study, we collected data from 505 women with surgically/histologically confirmed diagnosis of endometriosis and 505 matched controls. Study participants were recruited prospectively in hospitals and doctors' practices in Switzerland, Germany and Austria. Using a detailed questionnaire, the study investigated work-life and career choices of study participants. MAIN OUTCOME MEASURES Associations between endometriosis/disease symptoms and limitations in career development as well as ability to work. RESULTS Women with endometriosis were less often able to work in their desired profession than women from the control group (adjusted OR=1.84, 95% CI: 1.15 to 2.94, R2=0.029, p=0.001) and they had to take health-related limitations into consideration in their career decisions to a significantly higher degree than women in the control group (OR=4.79, 95% CI: 2.30 to 9.96, R2=0.063, p<0.001). Among women with endometriosis, chronic pain was significantly associated with increased sick leave (OR=3.52, 95% CI: 2.02 to 6.13, R2=0.072, p<0.001) as well as with loss of productivity at work (OR=3.08, 95% CI: 2.11 to 4.50, R2=0.087, p<0.001). CONCLUSIONS Endometriosis is associated with impairment of professional life, in particular with regard to career choices. Further research to develop strategies to support endometriosis-affected women in realising professional opportunities is recommended. TRIAL REGISTRATION NUMBER NCT02511626; Pre-results

Steigerung der Fertilität mittels Lifestylemodifikation

Wie sich die Konzeptionschance durch die Frau selbst optimieren lässt In der Schweiz leidet jedes zehnte Paar an einer ungewollten Kinderlosigkeit. Die Konzeptionschance kann mittels Lifestylemodifikation optimiert werden. Im besten Fall hat sich das Paar mit den folgenden Themen bereits auseinandergesetzt und auch entsprechende Schritte unternommen, bevor es in einer Kinderwunschsprechstunde vorstellig wird