Women Undergoing IVF Treatment Research Articles

P-398 Lower ectopic pregnancy prevalence with natural endometrial preparation in single euploid frozen embryo transfers

Abstract Study question Does the endometrial preparation approach for an euploid-frozen embryo transfer have an impact on the incidence of an ectopic pregnancy? Summary answer The natural cycle endometrial preparation approach seems to have a lower incidence of ectopic pregnancies compared to a hormonal replacement therapy cycle. What is known already Ectopic pregnancy (EP) is an uncommon complication of pregnancy and is associated with significant morbidity. IVF pregnancies have been implicated as a risk factor, but this finding is mostly confounded by multiple embryo transfer and complicated medical history of women undergoing IVF treatment (tubal disease, surgery, endometriosis, etc.). Recent studies have suggested that frozen embryo transfer may reduce the risk of EP, but it is not yet known whether embryo ploidy status and different endometrial preparation regimens affect the risk of EP. Study design, size, duration Retrospective cohort of 1517 pregnancies from 2607 single euploid frozen embryo transfers. Comparator estimates were estimated using multiple large cohort studies in the literature including 58,203,239 pregnancies from unselected cohorts and 220,167 pregnancies from IVF-treated women with the transfer of non-tested embryos. Participants/materials, setting, methods The rate of ectopic per pregnancies were compared to ectopic rate derived from multiple cohorts of IVF-treated women and population level reports of unselected pregnancies (natural conception and IVF). Comparator estimates were obtained with proportion meta-analyses using generalized linear mixed models. Factors associated with ectopic pregnancies were investigated with mixed-effects logistic regression analyses. Main results and the role of chance EP rate in our cohort was 10/1000 pregnancies (95% CI: 5 to 16 per 1000) resulting from single euploid embryo transfers (1.1%, 16/1517). The observed prevalence of EP was 12/1000 pregnancies (95% CI: 6.8 to 21 per 1000) in unselected cohorts and 14/1000 pregnancies (95% CI: 13 to 15 per 1000) after IVF-treatment. Ectopic rate in our study was not significantly different than rates reported in the literature from unselected and IVF pregnancies (P = 0.579 and 0.223, respectively). There were no significant differences between women with ectopic pregnancies and those with clinical pregnancies in terms of age (33.6±5.5 vs. 35.1±5.2 years, P = 0.290), BMI (26.7±4.8 vs. 25.8±4.6 kg/m2, P = 0.475) and serum AMH levels (3.3±2.9 vs. 3.4±3.9 ng/mL, P = 0.854), nor between the quality of embryo transferred between top, good, fair and poor (1.8% vs 0.7% vs 1.9% vs 0.9%, p = 0.088, 0.997 and 0.508 respectively). Ectopic rates were also similar between women with history of cesarean section (1.1% vs 1.0%, P = 0.847) or isthmocele (1.0 vs 1.1%, P = 0.857). There were less ectopic pregnancies following transfers with natural endometrial preparation (0.5 vs 1.5%, natural vs programmed) and the effect showed statistical significance in multivariable analyses (OR: 0.28, 95% CI: 0.06 – 0.88, P = 0.049). Limitations, reasons for caution Small sample size as well as infrequent occurrence of the studied event reduces the power of our study to detect small but clinically meaningful effects with statistical significance. Wider implications of the findings We did not observe a lower than reported prevalence of EP among euploid embryo transfer. However, rate of EP was significantly lower in natural endometrial preparation cycles compared to preparation with exogenous hormones, indicating that a natural cycle might have a protective effect against the development of an ectopic pregnancy. Trial registration number Not applicable

The Psychological Effects of Hormonal Treatment on Women Under IVF Treatment: A Comprehensive Review

This comprehensive review delves into the intricate world of assisted reproductive technologies (ART) and hormonal treatments, exploring their profound psychological effects on women undergoing IVF treatment. The psychological distress of infertility, combined with the demanding nature of ART, has been widely acknowledged, yet a comprehensive examination of the psychological impacts has remained elusive. This study examined the psychological repercussions of hormonal medications used in IVF, addressing the complex interplay of hormones and their effects in each stage of the IVF process. This review followed PRISMA guidelines and included studies from PubMed, Google Scholar, and ScienceDirect. A total of nine papers were collected. The findings of this study identified that depression, anxiety, mood swings, irritability, sleep disturbances, and cognitive changes were the most commonly seen medically induced psychological effects among the IVF patients. This review offers a holistic understanding of the psychological intricacies of IVF treatment, highlighting the imperative need for a more comprehensive approach to address the emotional wellbeing of individuals undergoing fertility procedures.

Adherence to dietary recommendations mediates the effect of affective temperaments on infertility treatment outcomes

Affective temperaments have been shown to robustly affect infertility treatment success. However, identification of possible mediating factors through which they exert their influence is still lacking. A growing number of results suggest that adherence to recommended treatments may be such a mediator, on the one hand, because affective temperaments are known to influence adherence and, on the other hand, because non-adherence negatively influences the treatment outcome. Recommended treatment of infertility involves, beyond medications, dietary and lifestyle changes. The aim of this retrospective cohort study was to evaluate whether adherence to physician-prescribed diet and physical activity recommendations mediates the effect of affective temperaments on infertility treatment outcomes. Among 308 women who underwent infertility treatment in an Assisted Reproduction Center, affective temperaments, adherence to diet, adherence to physical exercise, and infertility treatment success (clinical pregnancy) were assessed besides detailed medical history and demographic parameters. Associations between affective temperaments, adherence to diet and recommended physical activity, and assisted reproduction outcomes were analyzed using generalized linear models and causal mediation analysis. Adherence to physical activity didn’t have an effect, but diet adherence increased the odds of infertility treatment success by 130% suggesting its role as a potential mediator. Based on causal mediation analysis, higher depressive and anxious temperament scores were directly associated with 63% and 45% lower odds of achieving clinical pregnancy, respectively, with effects not mediated by diet adherence. Higher irritable temperament scores indirectly decreased the odds of achieving clinical pregnancy by 14%, mediated by diet adherence; while higher cyclothymic temperament scores decreased the odds of achieving clinical pregnancy both directly by 51% and indirectly, mediated by diet adherence by 11%. Our results suggest that diet adherence mediates the mechanism by which irritable and cyclothymic affective temperaments influence IVF treatment success. Since adherence is a modifiable risk factor of infertility treatment success, screening for affective temperaments may help to identify potentially high-risk non-adherent patient groups and offer patient-tailored treatment, which may help increase the chances of a successful pregnancy and live birth in women undergoing IVF treatment.

Examining the association between coping strategies and perceived social support among Vietnamese infertile women undergoing IVF treatment

ABSTRACT The purpose of the study was to examine the association between coping strategies and perceived social support among women diagnosed with infertility and undergoing IVF treatment. A total of 383 Vietnamese women were invited to participate in this study. Participants completed a questionnaire consisting of The Multidimensional Scale of Perceived Social Support, the Copenhagen Multi-centre Psychosocial Infertility coping scales and the Fertility Problem Inventory, and other relevant questions. The results reveal that coping strategies significantly predict some specific types of perceived social supports among women undergoing IVF treatment. Specifically, passive-avoidance coping (PAC) and active-avoidance coping (AAC) predicts a decrease in receiving support from family and friends, whereas active-confronting coping (ACC) predicts an increase in receiving support from these two sources of support. Women who demonstrate increased meaning-based coping (MBC) received all three sources of support including family, friends, and significant others support. Despite some limitations, this study is useful in understanding how coping strategies among women undergoing IVF treatment affects the social support received in the Vietnamese social context. It also emphasizes the importance of psychological support for women facing IVF treatment distress.

Effectiveness of psychotherapeutic nursing intervention on infertility stress, uncertainty, anxiety and implantation rate among women undergoing in-vitro fertilization treatment: A single centre pilot randomized controlled trial.

Background: Within the realm of mental distress experienced by women who are unable to conceive, tension, uncertainty, and anxiety are prevalent concerns. The multitude of unpredictable elements that occur during IVF treatment process can cause anxiety and stress. This unpleasant feeling has an impact on the psycho-neurological pathways of women who are unable to conceive. As a consequence, fertilisation and implantation are inhibited, leading to adverse effects on pregnancy. The individual's experience will vary depending on the extent of social support, the coping mechanisms employed, the quality of the marital connection, and the level of stress caused by infertility. Material and method: The study was carried out on 20 women undergoing IVF treatment. Participants were selected by simple random sampling technique. (COMPI) Fertility Problem Stress Scale, Uncertainty Scale for Infertile Women and Short Version of the Spielberger State—trait Anxiety Inventory were used to assess the level of stress, uncertainty and anxiety. Results: The findings of the current study indicate that 80% of women undergoing IVF in the experimental group experienced a moderate degree of stress prior to the intervention. However, this percentage decreased to 60% after receiving intervention. In case of uncertainty maximum of women had mild level of uncertainty and it remain unchanged in experimental group after intervention However, there was a significant decrease in anxiety levels (both STAIS and STAIT) in the experimental group following the intervention. Participants that received psychotherapeutic nursing intervention showed a higher rate of implantation. Conclusion: Psychotherapeutic nursing intervention can decrease the anxiety among women undergoing in vitro fertilisation treatment and also enhance the implantation rate.

Sleep quality, perceived stress and associated factors in women undergoing IVF treatment: short-term longitudinal study.

Despite limited studies in the literature, it is hypothesised that lifestyle factors are modifiable habits that have an impact on couples' fertility health. However, the relationship between sleep quality and infertility is an area that needs to be clarified. To determine sleep quality and associated factors in women receiving in vitro fertilisation treatment and to evaluate the changes in sleep over the treatment cycle. This is a longitudinal descriptive study conducted on 158 women in two infertility centres in Izmir, Turkey. Data were collected using the Personal Introduction Form, Pittsburgh Sleep Quality Index, Visual Analogue Stress Scale, and Physical Symptoms List. Data were collected during three different treatment periods: beginning of the in vitro fertilisation trial, oocyte pick-up day and the postembryo transfer period. The sleep quality score of women progressively decreased as treatment progressed (p < .001). A strong positive correlation was determined between stress and sleep quality (p < .001). Additionally, advanced age, low education level, shift work, prolonged treatment and economic distress were associated with poorer sleep quality (p < .001). In addition, breast fullness, abdominal distension, and pain (p < .001) observed until the oocyte pick-up day, as well as nausea and fatigue during the postembryo transfer period (p < .001), were identified as physical symptoms affecting sleep quality. This article provides information on sleep quality during in vitro fertilisation and guides healthcare professionals to encourage and improve women's sleep quality.

Affective temperaments show stronger association with infertility treatment success compared to somatic factors, highlighting the role of personality focused interventions

Infertility has a multifactorial background, where, besides somatic factors, psychological contributors also play a role in development and outcome. While affective temperaments have been associated with development, course, and outcome as well as treatment success in various somatic conditions, their association with infertility and its treatment has not been investigated so far. The purpose of our retrospective cohort study was to evaluate the influence of affective temperaments on fertility treatment outcomes. Among 578 women who underwent infertility treatment in an Assisted Reproduction Centre in Budapest, Hungary, treatment success, detailed medical history, and demographic parameters were recorded, and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A) was administered. Possible predictors of assisted reproduction outcome were analyzed using multivariate logistic regression models, followed by a receiver operating curve (ROC) analysis in order to define ideal affective temperament cut-off values for clinical applicability. Aside from age, BMI, and previous miscarriage, cyclothymic scores > 4 (OR = 0.51 CI 0.35–0.74, p < 0.001), depressive scores > 9 (OR = 0.59 CI 0.4–0.87, p = 0.009) and anxious scores > 9 (OR = 0.45 CI 0.31–0.66, p < 0.001) significantly decreased the odds of clinical pregnancy by 49%, 41% and 55%, respectively. Irritable and hyperthymic temperaments, as well as other somatic and socio-economic factors had no effect on infertility treatment outcomes. The results suggest that affective temperaments may be related to the outcome of infertility treatments. Thus, screening for affective temperaments may help identify high-risk patient groups and offer patient-tailored treatment, which may increase the chances of a successful pregnancy and live birth for women undergoing IVF treatment.

Counseling Elective Egg Freezing Patients considering Donation of Unused Surplus Frozen Eggs for Fertility Treatment.

The majority of women who freeze their eggs for non-medical or social reasons, commonly referred to as elective egg freezing (EEF), do not eventually utilize their frozen eggs. This would result in an accumulated surplus of unused frozen eggs in fertility clinics worldwide, which represents a promising source of donation to infertile women undergoing IVF treatment. Rigorous and comprehensive counseling is needed, because the process of donating one's unused surplus frozen eggs involves complex decision-making. Prospective EEF donors can be broadly categorized into those who have achieved motherhood and those who remained childless and have given up on motherhood aspirations. A two-step systematic counseling protocol is proposed. Firstly, it is imperative to verify and ensure that these women do not want to conceive any children with their surplus frozen eggs before proceeding with further counseling and signing ofconsent forms. Secondly, various motivating and dissuading factors in the donation of unused surplus frozen eggs should then be comprehensively discussed with egg freezers to facilitate informed decision-making. Key motivating factors for donation include reciprocity in wanting to share the joys of motherhood among egg freezers who already have children, goodwill to help others in need, and avoiding the wastage of surplus frozen eggs after expending so much money, time, and effort. Key dissuading factors include fear of accidental incest between natural and unknown donor-conceived offspring, as well as apprehension of unexpected future contact with unknown donor-conceived offspring due to either donor anonymity being abolished in their jurisdiction or widespread consumer DNA testing.

Detection of GSTM1—null Genotype in Women Undergoing IVF Treatment

Detection of GSTM1—null Genotype in Women Undergoing IVF Treatment

The impact of relationship status on IVF patients’ quality of life

ABSTRACT Infertility treatments are emotionally taxing and include invasive and time-consuming procedures over extended periods of time. In light of the growing numbers of single mothers by choice, the objective of this study was to apply the Conservation of Resources Theory in the context of infertility care and examine whether relationship status constitutes a psychological resource that buffers the decline in quality of life during IVF treatments. We used the FertiQol questionnaire to compare the quality of life of IVF patients between 422 patients who are involved in a couple relationship (“attached”) and 117 patients who are not (“unattached”). Results show that the total FertiQol was significantly higher among the attached participants; the Core FertiQol and the Treatment FertiQol were rated higher by the “attached.” No significant differences were found between the attached and unattached for the Emotional and Social subscales. “unattached” participants report significantly lower levels of quality of life in the “mind-body” and “treatment tolerability” subscales than the “attached” participants. It is concluded that being involved in a long-term couple relationship is to be seen as a resource that buffers the decline in quality of life of infertile women undergoing IVF treatments.

Association between ambient temperature exposure and pregnancy outcomes in patients undergoing in vitro fertilization in Shanghai, China: a retrospective cohort study.

Does ambient temperature exposure affect outcomes including clinical pregnancy and live birth in women undergoing IVF? Both extreme cold and hot ambient temperatures were significantly associated with adverse pregnancy outcomes of IVF cycles. Heat exposure has been linked to adverse pregnancy outcomes worldwide. However, the effect of ambient temperature on infertile women undergoing IVF treatment is unclear. A retrospective cohort study was conducted from a database of 3452 infertile women who underwent their first fresh or frozen embryo transfer in the Shanghai First Maternity and Infant Hospital from April 2016 to December 2020. Daily mean ambient temperature exposure for each patient was obtained based on their residential address. Temperature-stratified multiple logistic regression analysis was performed to investigate associations between temperature exposure and pregnancy outcomes after controlling for confounders. Vulnerable sub-groups were identified using forest plots. The clinical pregnancy rate and live birth rate were 45.7% and 37.1%, respectively. Regarding clinical pregnancy, a higher temperature during cold weather was significantly associated with a higher pregnancy rate in the period about 11 weeks before ovarian stimulation (adjusted odds ratio (aOR) = 1.102, 95% CI: 1.012-1.201). Regarding live birth, an increased temperature during cold weather was significantly related to a higher live birth rate in the period after confirmation of clinical pregnancy or biochemical pregnancy, with the aORs of 6.299 (95% CI: 3.949-10.047) or 10.486 (95% CI: 5.609-19.620), respectively. However, a higher temperature during hot weather was negatively associated with the live birth rate in the periods after confirmation of clinical pregnancy or biochemical pregnancy, with the aORs at 0.186 (95% CI: 0.121-0.285) or 0.302 (95% CI: 0.224-0.406), respectively. Moreover, the decline in live birth rates during cold and hot weather was accompanied by increased rates of early miscarriage (P < 0.05). Stratified analyses identified susceptibility characteristics among the participants. Climate monitoring data were used to represent individual temperature exposure levels according to the patient's residential address in the study. We were not able to obtain information of personal outdoor activity and use of indoor air conditioners in this retrospective study, which may affect actual temperature exposure. This study highlights that the ambient temperature exposure should be taken into account during IVF treatment and afterwards. There is a need to be alert to extremes in cold and hot ambient temperatures, especially during the period of follicle development and pregnancy. With this knowledge, clinicians can scientifically determine the timing of IVF treatment and reinforce patients' awareness of self-protection to minimize adverse pregnancy outcomes associated with extreme temperatures. This work was supported by a grant from the Clinical Research Plan of Shanghai Hospital Development Center [SHDC2020CR4080], a grant from the Science and Technology Commission of Shanghai Municipality [19411960500], and two grants from the National Natural Science Foundation of China [81871213, 81671468]. B.W.M. is supported by a NHMRC Investigator grant (GNT1176437). B.W.M. reports consultancy for ObsEva, and research grants from Merck KGaA, Ferring and Guerbet. The other authors have no conflict of interest to declare. N/A.

Detection of zeb1 Gene in Granulosa Cells in Women Undergoing IVF Treatment.

ZEB1 plays a role in epithelial-to-mesenchymal transition and acts as a repressor of E-cadherin, TGF-β, and Wnt/β-catenin. Since ZEB1 protein is expressed in estrogen-responsive tissues, and expression of the gene in the normal ovary and endometrium is positively correlated with high estrogen levels, we performed a direct analysis of granulosa cell samples to determine whether there are any significant changes in zeb1 expression during folliculogenesis. ZEB1 expression levels were measured in the granulosa cells of 56 infertile women undergoing IVF treatment. RNA extraction from granulosa cells was performed along with reverse transcription quantitative polymerase chain reaction (RT-qPCR) with SYBR Green I to determine zeb1 gene expression levels. Statistical analysis was performed by using t-test, while possible correlations of the expression of ZEB1 protein with body mass index (BMI), age, number of oocytes, and oocyte maturation were investigated. Zeb1 gene expression levels correlate significantly with body mass index (BMI) and age, but not with oocyte number and oocyte maturation stage. Obese women demonstrate a higher expression level of zeb1 gene compared to normal and overweight women. Moreover, zeb1 gene is overexpressed in women aged 35-40 years old and is under-expressed in women >40 years old. ZEB1 expression should be further investigated as it may unveil new potential findings of the zeb1 gene's role in female fertility and its use as a biomarker in fertility workups.

Phytoestrogens Present in Follicular Fluid and Urine Are Positively Associated with IVF Outcomes following Single Euploid Embryo Transfer

The impact and safety of phytoestrogens, plant-derived isoflavones with estrogenic activity predominantly present in soy, on female reproductive health and IVF outcomes continues to be hotly debated. In this prospective cohort study, 60 women attending IVI-RMA New Jersey undergoing IVF with single frozen embryo transfer (SET/FET) of good-quality euploid blastocyst after PGT-A analysis were recruited. Concentrations of two phytoestrogens (daidzein and genistein) in follicular fluid (FF) and urine (U) were measured by UPLC–MSMS, both collected on vaginal oocyte retrieval day. These measurements correlated with IVF clinical outcomes. In models adjusted for age, BMI, race/ethnicity, and smoking status, higher FF phytoestrogen concentrations were significantly associated with higher serum estradiol, enhanced probability of implantation, clinical pregnancy, and live birth. Moreover, higher urine phytoestrogen concentrations were significantly associated with improved oocyte maturation and fertilization potential and increased probability of clinical pregnancy and live birth. Finally, higher FF and urine phytoestrogen concentrations were associated with a higher probability of live birth from a given IVF cycle. Our results suggest that dietary phytoestrogens improved reproductive outcomes of women undergoing IVF treatment. However, additional prospective studies are needed to optimize the use of phytoestrogens to further enhance reproductive outcomes and/or protect against reproductive insults.

O-146 Oocyte donation does not increase live birth rates in young women suffering from recurrent pregnancy loss

Abstract Study question Does oocyte donation improve reproductive outcomes in recurrent pregnancy loss (RPL) patients? Summary answer Oocyte donation increases live birth and reduces miscarriage rates in RPL women older than 35, but it does not improve reproductive outcomes in younger patients. What is known already Recurrent pregnancy loss (RPL) is defined as 2 or more pregnancy losses prior to 20-24 weeks of gestation and has an incidence of approximately 1 to 2% in couples trying to conceive. Known risk factors for RPL are embryo aneuploidy, advanced maternal age (AMA), previous miscarriages, uterine abnormalities, parental chromosomal abnormalities, antiphospholipid syndrome, endocrine factors, such as thyroid function or obesity, and thrombophilia. However, 50-70% of patients suffering from RPL do not present any known risk factor, making the management of idiopathic RPL patients particularly challenging for ART clinicians. Study design, size, duration This is a cohort retrospective study involving 2 centers. Charts from 18,273 women undergoing IVF treatment between 2011 and 2020 were reviewed. A total of 912 patients (5%) met the definition of RPL and were classified into study groups based on their age and oocyte origin: ≤35 years old receiving oocyte donation (n = 39) or using their own oocytes (n = 35), and AMA women using donor eggs (n = 716) or their own (n = 122). Participants/materials, setting, methods Demographic variables analysed included known risk factors, number of transferred embryos, day of embryo transfer (3 vs 5) and sperm origin (partner/donor). Differences in biochemical, clinical, ongoing pregnancy, miscarriage and live birth rates were assessed by Pearson’s Chi-squared or Fisher’s exact test. P-values &amp;lt;0.05 were considered significant. Main results and the role of chance RPL patients had 2.77±1.27 pregnancy losses overall (2.76±1.37 in women ≤35 and 2.77±1.26 in patients &amp;gt;35). Most RPL patients (91.9%) were of AMA. Other RPL-associated risk factors, including uterine malformations, previous pregnancy losses, chromosomal abnormalities and thrombophilia were identified in 207/912 patients (22.7%). Interestingly, these were more frequent in patients &amp;lt;35 (37.8% vs 21%, p = 0.001). Young RPL women presented higher rates of karyotype abnormalities than older patients (17.6% vs 3.8%, p &amp;lt; 1x10-04), while showing a similar incidence of uterine abnormalities (14.9% vs 12.9%, p &amp;gt; 0.63) and thrombophilia (4.1% vs 4.7%, p &amp;gt; 0.81). RPL patients &amp;gt;35 preferentially underwent oocyte donation (85.4% vs 52.7%, p &amp;lt; 1x10-04), which led to significantly higher biochemical (52.5% vs 17.1%, p &amp;lt; 1x10-04), clinical (42.4% vs. 8.5% p &amp;lt; 1x10-04), ongoing pregnancy (37.9% vs 5.1%, p &amp;lt; 1x10-04), live birth (32% vs 4%, p &amp;lt; 1x10-04) and lower miscarriage rates (10.5% vs 40%, p = 0.0186) than in autologous cycles. In contrast, RPL patients &amp;lt;35 had similar reproductive outcomes: biochemical (41% vs. 52.9), clinical (28.2% vs. 37.1%), ongoing pregnancy (25.6% vs 29.4%), live birth (25.6% vs 26.4%) and miscarriage rates (9% vs 23%), regardless of oocyte origin (donated vs own, p &amp;gt; 0.05 for all cases). Importantly, this was also true for a small subgroup of idiopathic young RPL patients (n = 13). Limitations, reasons for caution The main limitation of this study is its retrospective nature, which does not allow for full elucidation of all potential confounders. The number of young RPL patients undergoing oocyte donation may be too low to draw significant conclusions. Wider implications of the findings RPL can be resolved in AMA patients by using donor oocytes, which points to key roles of oocyte quality and aneuploidy underlying RPL aetiology. However, RPL is not ameliorated by oocyte donation in young women, suggesting an endometrial/systemic origin and highlighting the need to further study mechanisms driving this disorder. Trial registration number Not applicable

P-673 Women exposed to higher levels of DEHP display altered microRNA expression profile in the pre-ovulatory follicular fluid

Abstract Study question Can higher concentrations of di-2-ethylhexyl phthalate (DEHP) in follicular fluid (FF) lead to an altered microRNA expression profile? Summary answer The present study indicates the upregulation of miR-203a-3p, miR-150-5p and miR-28-3p in the follicular fluid of women with higher DEHP concentrations (FDR&amp;lt;0.05). What is known already Women are exposed daily to endocrine-disrupting chemicals (EDCs) such as phthalates which can be found in hundreds of personal care products and plastic items. In studies of rodents exposed to certain phthalates, high doses have been shown to change hormone levels, disrupt folliculogenesis and cause birth defects. Recently, we reported a strong inverse association between DEHP metabolites and ovarian sensitivity index (OSI) in females undergoing ART treatment. Several mechanisms have been proposed to explain the association between DEHP and fertility in rodents, however not much is known about the mechanisms in humans. Study design, size, duration FF was collected from 96 women undergoing IVF treatment after controlled ovarian stimulation during ovarian puncture. 48 participants from Estonia were recruited at Nova Vita Clinic AS in Tallinn, Estonia in 2019 and 48 participants from Sweden were recruited at Carl von Linnekliniken in Uppsala, Sweden in 2016. In both cohorts, patients signed a written informed consent form. Both cohorts were matched for age, BMI, parity and the number of previous IVF treatments. Participants/materials, setting, methods DEHP metabolite concentrations in the FF samples were measured in our earlier study by LC-MS/MS. Cell free RNA was extracted from FF samples with Qiagen miRNeasy Micro kit, sequencing libraries were prepared with QIAseq miRNA library kit and sequenced on Illumina NextSeq 550 instrument. Differential miRNA expression analysis was performed with the DESeq2 package. Pathway enrichment analysis for differentially expressed miRNA targets was conducted with the miEAA tool integrated with WikiPathways. Main results and the role of chance In total, 465 miRNAs were observed at least twice in ≥ 24 samples. Differential expression analysis was conducted between DEHP-high and DEHP-low groups in combined cohorts using the cohort as a covariate. 16 miRNAs were found to be differentially expressed between DEHP groups with FDR&amp;lt;0.1. Three miRNAs: miR-203a-3p, miR-150-5p and miR-28-3p, were differentially expressed with FDR&amp;lt;0.05 and were more abundant in women with high DEHP-levels in both cohorts. Of these, miR-203a-3p was negatively correlated with OSI (Pearson R = -0.27, p = 0.0089). Six miRNAs (miR-10b-5p, miR-112-5p, miR-132-5p, miR-203-3p, miR-205-5p and miR-27-3p) were found to have predicted targets in the androgen receptor signalling pathway. Limitations, reasons for caution The miRNAs found in this study need to be validated in a larger set of patients as a cohort-dependent difference in the results was observed. There is a need for further functional studies to investigate miRNAs as possible mediators of the association between DEHP and ovarian sensitivity index. Wider implications of the findings The current study presents evidence that DEHP exposure alters the expression of FF miRNAs which are associated with androgen receptor signalling. These results provide novel evidence of the potential influence of endocrine-disrupting chemicals on female reproduction. Trial registration number NA

P-436 Non-Essential Trace Elements in women’s biofluids are associated with worse IVF outcomes in euploid single embryo transfer cycles.

Abstract Study question What is the non-essential trace element exposure impact on the reproductive outcomes of women undergoing IVF treatment? Summary answer Increased blood and urinary non-essential trace element concentration were associated with worse IVF outcomes. What is known already Lower fertility rates have been observed in recent decades in industrialized regions, increasing the need for assisted reproductive techniques. Factors responsible for this decline in human fertility include exposure to non-essential trace elements. Since these elements have no known biological functions, they are considered detrimental to the normal function of the organism. The most common elements evaluated so far have been those traditionally considered toxic, such as heavy metals and metalloids (mercury, lead, cadmium and arsenic), for which inconsistent negative associations with different IVF treatment variables have been described. Study design, size, duration 51 women who underwent an euploid single-embryo transfer (SET) after PGT-A analysis, were included. Nine non-essential elements (barium (Ba), strontium (Sr), rubidum (Rb), arsenic (As), tin (Sn), cesium (Cs), mercury (Hg), lead (Pb), antimonium (Sb)) were measured in follicular fluid (FF), whole blood (B) and urine (Urine-VOR), all collected at vaginal oocyte retrieval day (VOR), and urine collected at transfer day (Urine-T). These measurements were correlated with IVF clinical outcomes. Participants/materials, setting, methods Quantification of non-essential elements in the four biofluids were performed by inductively coupled plasma mass spectrometry (ICP-MS). Urine concentrations were normalized by creatinine, quantified by Jaffe reaction. Generalized linear models were employed to explore ovarian response variables and embryological IVF outcomes (associations, estimated as percentile 20th to 80th increase (95% confidence intervals (CI)). Associations with IVF clinical outcomes were estimated by odds ratio (95%CI). Both unadjusted and age-BMI-race-smoking-adjusted models were applied. Main results and the role of chance Participants had a median age of 39 years [Inter Quartile Range (IQR): 31.37, 36.50] and BMI of 22.97 kg/m2 [IQR: 20.63, 25.12], and 50% had never smoked. In adjusted models, significantly negative associations were found between blood Hg concentration and relative frequency of fertilized embryos [0.73 (0.56,0.96), p = 0.024], blastocyst arrival [0.64 (0.44,0.93), p = 0.019], and euploid embryos [0.60 (0.37,0.98), p = 0.044]. We also found negative associations for urine-VOR Sn and blastocyst arrival [0.72 (0.53,0.98) p = 0.038] and euploid embryos [0.55 (0.39,0.77), p &amp;lt; 0.001]. In the case of urine-T, higher concentrations of St were associated with lower number of retrieved oocytes [0.71 (0.57,0.90), p = 0.006], relative frequency of mature oocytes [0.75 (0.62,0.90), p = 0.003], fertilized embryos [0.72 (0.62,0.83), p &amp;lt; 0.001], blastocyst arrival [0.68 (0.56,0.84), p &amp;lt; 0.001] and euploid embryos [0.83 (0.69,1.00), p = 0.048]. urine-T Cs was associated with lower proportion of mature oocytes retrieved [0.65 (0.42,0.99), p = 0.046] while both Rb and Cs was associated with lower proportion of euploid embryos [0.066 (0.44,0.99), p = 0.048; 0.55 (0.34,0.89), p = 0.019, respectively]. Regarding IVF clinical outcomes, in fully adjusted models, our results suggest that higher concentrations of As in urine-T were associated with lower probability of live birth [0.03 (0.00,0.36); p = 0.038] and reproductive goal (live birth/all participants) [0.03 (0.00,0.36); p = 0.038]. Limitations, reasons for caution Further studies are needed to confirm this association in greater populations, including the measurement of different element species. Wider implications of the findings Exposure and circulating levels of these non-essential elements have a significant impact on IVF outcomes. These data highlight the need to further study non-essential trace elements to identify and characterize how may be affecting IVF. Trial registration number not applicable

An assessment of coping with infertility stress and eating disorders in women undergoing IVF treatment

An assessment of coping with infertility stress and eating disorders in women undergoing IVF treatment

The Association Between Spirituality and Hope Among Turkish Women Undergoing Infertility Treatment.

The aim of this study was to determine the effect of spirituality on the levels of hope in women undergoing infertility treatment. This cross-sectional study was completed with the participation of 150 women undergoing IVF treatment at a university hospitalin Kocaeli. In this study the women's spiritual well-being levels were high, and their hope levels were above the average score. Significant correlations were found between hope, spirituality, educational status, and age. Since attempts to boost hope will increase the chance of success in treatment, it is thought that factors affecting the level of hope should be determined and addressed. It is also thought that health professionals can apply hope therapy to women and take initiatives to provide spiritual support.

The effect of endometrial scratching on reproductive outcomes in infertile women undergoing IVF treatment cycles

This study was a Randomised Controlled Trial aiming to evaluate the effect of Endometrial Scratching (ES) on fertility rate. Participants were primary infertile women undergoing IVF treatment. ES for the intervention group was done using endometrial aspiration in the luteal phase of the cycle before embryo transfer. In both groups, 2–3 8-celled embryos were transferred after endometrial preparation by Oestrogen and Progesterone. There were no significant differences between the two groups in terms of age, BMI and endometrial thickness (ET). No significant differences were found between intervention and control groups in chemical pregnancy rate (p = 0.410), clinical pregnancy (p = 0.822), the number of abortions (p = 0.282) and the implantation rate (p = 0.777). Local ES had no significant effects in improving the IVF success rate and reducing the embryo abortion rate. Impact statement What is already known on this subject? Endometrial scratching (ES) is a local injury to the endometrium that was assumed to affect implantation in IVF and IUI cycles positively. However, various studies have shown conflicting results on this matter. What do the results of this study add? Local ES had no significant effects on improving the IVF success rate and reducing the embryo abortion rate in patients with the first IVF cycle. What are the implications of these findings for clinical practice and/or further research? Larger clinical trials can measure the usefulness of ES with higher powers. However, this study, along with other clinical trials, can help evaluate the ES effect in future meta-analyses.

Low-grade inflammation is negatively associated with live birth in women undergoing IVF

Research questionIs low-grade inflammation, detected by C-reactive protein (CRP), a marker of IVF outcome addressing both blastocyst quality and pregnancy outcome? DesignThis sub-study of a multicentre randomized controlled trial included 440 women undergoing IVF treatment with a gonadotrophin-releasing hormone (GnRH) antagonist protocol. Serum CRP was measured on cycle day 2–3 (baseline) and on the day of ovulation triggering. The association between CRP concentrations and reproductive outcomes (number of retrieved oocytes, number of good-quality blastocysts, pregnancy, pregnancy loss and live birth), were analysed, adjusting for relevant confounders. ResultsA negative association was found between higher baseline CRP concentrations and live birth rate (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.62–0.96, P = 0.02) and higher CRP concentrations at baseline were associated with pregnancy loss among women who conceived (OR 1.37, 95% CI 1.07–1.76, P = 0.01). When testing for a specific cut-off, CRP concentrations above 2.34 (the highest quartile) were more likely to be associated with pregnancy loss (P = 0.02) and a lower chance of live birth (P = 0.04) compared with the lowest quartile. No associations were found between CRP concentrations and pregnancy outcomes on the day of ovulation triggering, and there were no associations between CRP concentrations and the number of good-quality blastocysts. ConclusionsHigher CRP concentrations at cycle day 2–3, before starting ovarian stimulation, are negatively associated with chance of live birth, possibly because of an increased risk of pregnancy loss. No association was found between the number of good-quality blastocysts and CRP concentration. More studies are needed to investigate the impact of low-grade inflammation.