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

Ibuprofen delays ovulation by several hours: prospective controlled study in natural cycles with HCG-triggered ovulation.

RESEARCH QUESTION Does ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), delay ovulation? DESIGN Two-stage, proof-of-concept, controlled study, assessing the percentage of non-ovulated follicles 42 h after HCG injection in patients taking ibuprofen. The intervention group consisted of women undergoing natural cycle IVF treatment taking ibuprofen 3 × 400 mg per day. The control group consisted of women undergoing timed sexual intercourse or intrauterine insemination. The proportion of patients with non-ovulated follicles in the ibuprofen group was first compared against a reference of 50% using a one-sample binomial test, and second against the proportion observed in the control group using an adjusted logistic regression. RESULTS A total of 26 women were recruited in the ibuprofen intervention group. Twenty-five patients were recruited in the control group. The proportion of patients with delayed ovulation observed (22/26 [84.6%]; 95% CI 65.1% to 95.6%) was significantly higher than the reference of 50% (P < 0.001). In the control group, the proportion of patients with delayed ovulation was 20.0% ([5/25], 95% CI 6.8% to 40.7%). Compared with the ibuprofen group, a significantly increased probability of a delayed ovulation was found in the ibuprofen intervention group (adjusted OR 22.72, 95% CI 5.77 to 115; P < 0.001). Of the 22 women with delayed ovulation, oocytes were retrieved in 20 women (90.9%) and all oocytes were mature (metaphase II). CONCLUSIONS Women trying to conceive should avoid non-selective NSAIDs around the time of ovulation. Ibuprofen or other NSAID can be used to delay ovulation for several hours in assisted reproductive technology and other infertility treatments if required

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

Comparison of male and female perspective in couples involved in sexual relationships and facing endometriosis

Background While the sexuality of patients with endometriosis is an established topic in research, the possible effect of endometriosis on partnership sexuality has come to the fore only recently. To improve counseling, more information is needed on how both partners experience sexuality in the context of endometriosis. Aim Previous research regarding endometriosis and sexuality normally focused on one partner to explore couples’ intimate relations, whereas this study provides a comparison on both partners’ perspectives on their common sexuality. Methods An overall 302 couples received a questionnaire based on the Brief Index of Sexual Functioning and Sexual History Form, which was modified by endometriosis specialists to better focus on endometriosis-specific aspects. To detect different perspectives on common sexuality within the couple, the Wilcoxon test and the Pearson chi-square test were performed. Outcomes Various aspects of couple sexuality were assessed by both partners to investigate divergent perspectives between the man and the woman within a couple. Results On one hand, male and female partners seem to have divergent perspectives on sexual satisfaction in general, desired frequency of sexual contacts, and the question of the female partner engaging in sexual activity despite discomfort. On the other, they have similar perspectives on who takes initiative in sexual contacts, satisfaction with variety in the sexual relationship, and the impact of sexual limitations on their satisfaction within the partnership. Clinical implications Endometriosis research addressing issues related to sexuality should include male partners; the same applies to consulting women with endometriosis in the context of their relationships rather than as individuals. Strengths and Limitations This is the first analysis conducted on a larger scale of data from both partners in couples dealing with endometriosis. As it provides quantitative information only, some qualitative information remains unexplored. Conclusion As both partners showed tendencies to overestimate their partners’ sexual satisfaction and had different perspectives on sensitive topics in sexuality, such as the female partner engaging in sexual activity despite discomfort, addressing sexual communication could be a starting point in counseling couples dealing with endometriosis

Dysmenorrhea in adolescents requires careful investigation of endometriosis—an analysis of early menstrual experiences in a large case-control study

Introduction Recent evidence shows that endometriosis, a significant cause of infertility, may already present in adolescents. Dysmenorrhea, often leading to school absences, is a key symptom of the maturing menstrual cycle but also of endometriosis. However, it is often perceived as “normal” and left untreated. In adolescents, laparoscopy, the standard procedure to diagnose endometriosis, is performed particularly cautiously. To improve reproductive health in adolescents, we evaluate associations between early menstrual experiences and endometriosis. Methods Retrospective data on early menstrual experiences from 563 women with surgically/histologically verified endometriosis and from 563 age-matched controls were compared. Study participants were recruited in Switzerland, Germany, and Austria. Information on menstrual experiences was collected via a structured questionnaire. Results The bivariate analysis showed that early menarche (p = 0.004), dysmenorrhea and negative memories of menarche (p &lt; 0.001) were significantly associated with a diagnosis of endometriosis. After controlling for confounders in bivariate regression analysis occurrence of dysmenorrhea (p = &lt;0.001, OR 5,74, 95% CI 3.82–7.22) especially with onset &gt;3 years after menarche ((p = &lt;0.001, OR 3.42, 95% CI 2.09–5.64) remained statistically significant predictors for diagnosis of endometriosis. Dysmenorrhea in mothers and mothers' perceived attitude towards menstruation were not associated with the occurrence of Endometriosis. Conclusions Dysmenorrhea and onset of dysmenorrhea at menarche or several years after it are strongly associated with the development of endometriosis. As mothers perceived attitudes towards menstruation show no significant association with their daughters' experiences, physical symptoms accompanying menarche and menstrual period pain in adolescents seem to be very reliable predictors in diagnosis of endometriosis. Therefore, dysmenorrhea in adolescents requires careful investigation of possible endometriosis, especially if it does not respond to medical management. Clinical trials registration The study was registered on ClinicalTrials.gov, identifier (NCT 02511626)

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

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