Ghanaian women's experiences of unsuccessful in-vitro fertilisation treatment, unravelling their meanings: a Heideggerian hermeneutic phenomenological study.

BACKGROUND: Women having experienced infertility over a period usually decide on an option for an invitro fertilisation treatment (IVF). However, in the quest to seek help and to be part of motherhood, they sometimes become unsuccessful in their fertility journey. The researchers aimed to explore the meanings and emotions attached to infertility and unsuccessful invitro fertilisation (IVF) treatment among Ghanaian women, as this area of inquiry is less explored in Africa and specifically in the Ghanaian context. METHODS: The study followed a qualitative approach and drew inspiration from the Heideggerian phenomenological philosophy and design. Six (6) women, aged between 29 and 40 years, who had experienced at least one unsuccessful IVF cycle, were purposefully selected from a private specialist fertility hospital in Kumasi, Ghana. One-on-one interviews were conducted with the participants, and the interviews were transcribed verbatim. The collected data was analyzed using Van Manen six-step framework, which helped to uncover the existential meanings and interpretations these women ascribed to their experiences. RESULTS: The results of the study revealed four main themes that were deemed essential aspects of meaning for the participants. These themes were: (1) Experiencing an Existential Faith and Hope. The participants described their journey through infertility and invitro fertilisation (IVF) treatment as a profound test of their existential faith and hope finding strength in maintaining a positive outlook despite the challenges and setbacks they faced., (2) Facing up to the Angst: This theme highlights the participants' courage in confronting the emotional dimensions of their struggles. The women acknowledged and confronted their anxieties, fears, and emotional distress associated with their infertility and unsuccessful IVF treatment., (3). Non-disclosedness: This theme refers to the participants' experiences of keeping their struggles with IVF treatment private, often due to societal and cultural factors. (4). Endured feelings of inadequacy of being-in-the-world-of-motherless: Participants expressed feelings of inadequacy, self-doubt, and a sense of being incomplete due to their inability to conceive and fulfill the societal role of motherhood. Their narratives revealed the profound impact of societal expectations on their self-perception and identity. CONCLUSION: The study's findings reveal insights into the experiences and interpretations of infertility and unsuccessful IVF treatment among Ghanaian women. Employing Heideggerian hermeneutics, the research elucidates the diverse existential, emotional, and societal aspects inherent in the struggles of infertility. The multifaceted nature of these women's journeys underscores the significance of a comprehensive approach to infertility care that recognizes the cultural, social, emotional, and existential dimensions of the IVF process. Additionally, the study emphasizes the necessity for culturally sensitive support systems and interventions to address the unique challenges faced by this population.

Psychosocial and environmental motivational key factors behind the parenthood desire in infertile couples at the time of COVID-19.

PURPOSE: To evaluate the main psychosocial motivational factors behind the increased adoption of IVF during the COVID-19 pandemic. METHODS: This prospective, multicenter, observational case-control study assessed the factors motivating infertile couples to pursue their first IVF treatment during the pandemic across various IVF clinics in Spain, Portugal, Italy, the USA, and Panama. A pre-pandemic control group and a post-pandemic participant group were surveyed. The study was conducted between November 2021 and January 2023. The increase in IVF cycles was analyzed, and an ad hoc survey was developed to explore the motivational factors driving IVF engagement. RESULTS: Most clinics reported a significant increase in IVF demand (5.5-8.7%) for all indicators, including the number of started ovarian stimulations, oocyte pickups, and embryo transfers, following the declaration of the pandemic. The extra time spent and the reduced workload were the most important motivations prompting women to pursue their first fertility treatment during the pandemic (time to spend in the couple's relationship-OR, 1.53; 95% CI, 1.06-2.20; p < 0.05; decreased workload-OR, 2.63; 95% CI, 1.11-6.24; p < 0.05). CONCLUSION: This study highlights that infertility remains a significant stressor for individuals, and the desire to resolve it is not hindered by catastrophic events like COVID-19. Open communication between partners about reproductive intentions, combined with reduced work-related stress, is a key factor influencing the initiation of fertility treatment. It is crucial to encourage couples to take timely action in facing infertility.

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

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.

Self-blame predicts anxiety and depression in infertile couples who opt for in vitro fertilisation (IVF) treatment.

The study examined the use of maladaptive coping strategies such as conflict, avoidance and self-blame in predicting anxiety and depression in couples undergoing IVF procedure. The target group consisted of 80 couples who started the IVF treatment at the Division of Obstetrics and Gynaecology, Ljubljana's University Medical Centre in Slovenia. The participants completed three scales: S/T Anxiety Inventory, CES Depression Scale, and Marital Coping Inventory. The results showed increased rates of depression compared to the normative population; 18% of women and 14% of men reported mild to moderate depression or the possibility of major depression. Women showed higher anxiety scores than men. Coping strategies predicted both depression and anxiety, with self-blame being the most toxic one. The study showed that self-blame is a coping strategy that should be properly addressed in the couples at the very outset of IVF treatment, to decrease emotional disorders and increase the likability of a succesful IVF medical procedures.

Presence of adenomyosis at MRI reduces live birth rates in ART cycles for endometriosis.

STUDY QUESTION: What is the impact of adenomyosis on the live birth rate (LBR) in women affected by endometriosis women undergoing ART? SUMMARY ANSWER: For women undergoing ART, the presence of adenomyosis at MRI, especially T2 high-signal intensity spots within the myometrium, has a negative impact on the LBR. WHAT IS KNOWN ALREADY: Adenomyosis is a common gynecological disease. The development of imaging techniques for the diagnosis has led to several adenomyosis phenotypes being described, and fertility issues appear to vary according to the characteristics of the lesions. What makes assessment of the impact of adenomyosis on fertility issues even more difficult is its frequent association with endometriosis, which is another known risk factor of infertility. Although data suggest that adenomyosis may worsen the ART prognosis, there is no clear consensus regarding the impact of adenomyosis on ART outcomes in women affected by endometriosis. STUDY DESIGN, SIZE, DURATION: This was an observational study that included phenotyped patients with endometriosis, aged between 18 and 42 years, who underwent IVF/ICSI treatment in a tertiary care center between June 2015 and July 2018. Only women who had undergone a pelvic MRI during the pre-therapeutic ART workup were retained for this study. The MRI data were interpreted by radiologists who had expertise in gynecological MRI. PARTICIPANTS/MATERIALS, SETTING, METHODS: A continuous series of 202 women affected by endometriosis was included. The women were monitored until four ART cycles had been completed, until delivery, or until discontinuation of treatment before the completion of four cycles. The primary outcome was the delivery of at least one live infant after up to four IVF/ICSI cycles. The patient and the MRI characteristics were compared between the women who achieved a live birth versus those who did not. MAIN RESULTS AND THE ROLE OF CHANCE: The patients' mean age was 32.5 ± 3.7 years. Deep infiltrating endometriosis was present in 90.1% (182/202) of the included population. Adenomyosis (lesions of the internal and/or the external myometrium) was found in 71.8% (145/202) of the included women. The cumulative LBR was 57.4% (116/202). The women who gave birth were significantly younger (32.0 ± 3.3 versus 33.3 ± 4.1, P = 0.026) and had significantly better ovarian reserve parameters (anti-Müllerian hormone levels, antral follicle count) than those who did not. The presence of adenomyosis, irrespective of the phenotype (76/116 (65.5%) versus 69/86 (80.2%), respectively, P = 0.022) and the presence of T2 high-signal intensity myometrial spots (27/116 (23.3%) and 37/86 (43.0%), respectively, P = 0.003) was significantly less frequent in the group of women who gave birth versus those who did not. After multivariate analysis, the presence of adenomyosis (odds ratio (OR): 0.48, 95% CI (0.29-0.99), P = 0.048) and the presence of T2 high-signal intensity myometrial spots (OR: 0.43, 95% CI (0.22-0.86), P = 0.018) were independently found to be associated with a decrease in the cumulative chance of live birth. LIMITATIONS, REASONS FOR CAUTION: The inclusion of patients from a referral center specialized in the management of women affected by endometriosis could constitute a selection bias, as these women may have had particularly severe forms of adenomyosis and/or endometriosis. A sensitive issue is that there is no consensual classification of adenomyosis and several lesions of adenomyosis can co-exist. Therefore, a comparison of fertility outcomes between women with and without adenomyosis is difficult to perform in practice. WIDER IMPLICATIONS OF THE FINDINGS: In women exhibiting endometriosis, the practitioner should perform an appropriate imaging workup to search for adenomyosis, identify prognostic factors, and personalize the patient management strategy in the setting of ART. STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained and there were no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Immersive virtual reality as tool to reduce anxiety during embryo transfer.

The use of Virtual Reality (VR) has gained wide acceptance in several scientific fields. It represents an innovative technological tool providing the experience to be immersed in a non-physical world putting on head-mounted displays that surround the users with images and sounds. To date, VR has been mainly employed in the healthcare sector for educational aims, in order to provide the learners with a new method of delivering simulations. However, its application to real clinical practice has recently generated beneficial effects for patients, especially for those who experience symptoms of psychological burden. Infertile couples often struggle with anxiety and depression which have a strong impact on life quality. Furthermore, the perspective to undergo long treatments with uncertain results and an history of failed attempts may contribute to enhance patients' negative feelings during In Vitro Fertilization (IVF) cycles until Embryo Transfer (ET). The role of VR in reducing pain and anxiety during outpatient hysteroscopy, hysterosalpingography and oocytes retrieval, has been recently investigated with satisfactory results in terms of reducing pain and anxiety levels. However, to date, inconclusive outcomes have been reported on pregnancy rate. Our study would discuss the existent literature on VR applied to current medical practice and infertility, proposing its beneficial impact on women anxiety during IVF cycle with ET.

Superannuation Access for IVF Purposes: Time for Reform?

Australia's superannuation system permits the early withdrawal of funds from superannuation accounts in limited circumstances. There has been a trend towards increasing use of the early withdrawal provisions to fund in vitro fertilisation (IVF) treatment through the broad "compassionate release" ground. A 2018 government report recommended tightening the relevant criteria for release, which would restrict release for IVF purposes to those suffering from a mental illness related to their childlessness. This article examines the impact of childlessness in those wishing to have children and concludes that the current release criteria should not be tightened in such a manner. However, the article suggests positive changes in the law to achieve greater compliance with the current law, which restricts early superannuation release to when a lack of alternative funding is unavailable.

Female age is associated with the optimal number of oocytes to maximize fresh live birth rates: an analysis of 256,643 fresh ART cycles.

RESEARCH QUESTION: What is the optimal number of oocytes retrieved at which maximum live birth rate is observed after fresh autologous assisted reproductive technology (ART) cycles for women of different ages? DESIGN: Retrospective cohort study of all fresh autologous ART aspiration cycles (n = 256,643) undertaken in Australia and New Zealand between 2009 and 2015. Primary outcome measure was live birth rate (LBR) (delivery of at least one liveborn baby at 20 weeks' gestation or over per fresh aspiration cycle). Cycles were grouped according to female age (<30, 30-34, 35-49, 40-44 and ≥45 years) and ovarian response (one to three, four to nine, 10-14, 15-19, 20-25 and ≥25 oocytes). Secondary outcome was incidence of ovarian hyperstimulation syndrome (OHSS) requiring hospitalization. RESULTS: At different oocyte yields, LBR per fresh aspiration cycle peaked and then declined at, depending on female age: <30 years: six to 11 oocytes (LBR 31-34%); 30-34 years: 11-16 oocytes (LBR 29-30%); 35-39 years: nine to 17 oocytes (LBR 21-24%); and 40-44 years: 15-17 oocytes (LBR 11-12%). The incidence of OHSS increased significantly with the number of oocytes retrieved, from 1.2% with 15 oocytes retrieved to 9.3% with 30 or more oocytes retrieved (P < 0.001). CONCLUSION: The optimal number of oocytes at which maximum LBR was observed in a fresh aspiration cycle was highly dependent on age. Because of the observational nature of the results, a cause-effect relationship between the number of oocytes retrieved and LBR should not be assumed; evidence from well-designed randomized control trials is required before clinical advice can be suggested.

Characterization of the Sperm Proteome and Reproductive Outcomes with in Vitro, Fertilization after a Reduction in Male Ejaculatory Abstinence Period.

Semen samples from men after a short ejaculatory abstinence show improved sperm quality and result in increased pregnancy rates, but the underlying mechanisms remain unclear. Herein, we report that ejaculates from short (1-3 h) compared with long (3-7 days) periods of abstinence showed increases in motile sperm count, sperm vitality, normal sperm morphology, acrosome reaction capacity, total antioxidant capacity, sperm mitochondrial membrane potential, high DNA stainability, and a decrease in the sperm DNA fragmentation index (p, < 0.05). Sperm proteomic analysis showed 322 differentially expressed proteins (minimal fold change of ±1.5 or greater and p, < 0.05), with 224 upregulated and 98 downregulated. These differentially expressed proteins are profoundly involved in specific cellular processes, such as motility and capacitation, oxidative stress, and metabolism. Interestingly, protein trimethyllysine modification was increased, and butyryllysine, propionyllysine, and malonyllysine modifications were decreased in ejaculates from a short versus, long abstinence (p, < 0.05). Finally, the rates of implantation, clinical pregnancy, and live births from in vitro, fertilization treatments were significantly increased in semen samples after a short abstinence. Our study provides preliminary mechanistic insights into improved sperm quality and pregnancy outcomes associated with spermatozoa retrieved after a short ejaculatory abstinence.

Personalized medicine for in vitro fertilization procedure using modeling and optimal control.

In vitro fertilization (IVF) is the most common technique in assisted reproductive technology and in most cases the last resort for infertility treatment. It has four basic stages: superovulation, egg retrieval, fertilization, and embryo transfer. Superovulation is a drug-induced method to enable multiple ovulation per menstrual cycle and key component towards a successful IVF cycle. Although there are the general guidelines for dosage, the dose is not optimized for each patient, and complications, such as overstimulation, can occur. To overcome the shortcomings of this general system, a mathematical procedure is developed which can provide a customized model of this stage regarding the size distribution of eggs (follicles/ oocytes) obtained per cycle as a function of the chemical interactions of the drugs used and the conditions imposed on the patient during the cycle, which provide a basis for predicting the possible outcome. Uncertainty and risk are modeled and included in optimal drug dosage decisions. This paper describes the theory, model, and the optimal control procedure for improving outcomes of IVF treatment for one of the four protocols used in real practice. The validation of the procedure is performed using clinical data from the patients previously undergone IVF cycles. Customized patient-specific model parameters are obtained by using initial two-day data for each patient. Subsequently, this model is used to predict the FSD for the remaining days of the cycle. This procedure was conducted for 49 patients. The results of the customized models are found to be closely matching with the observed FSD. These results thus validate the modeling approach and consequently its use for predicting the customized optimal drug dosage for each patient. Using the customized model and the optimized dosage, the FSD at the end of the cycle was determined. A small double-blind clinical trial was also conducted in India. The results from the trial show that the dosage predicted by using the model is 40% less than the suggestion made by the IVF clinicians. The testing and monitoring requirements for patients using optimized drug dosage is reduced by 72%. Work on the other three protocols and for patients in the USA is started and is showing promising results.

The number of oocytes associated with maximum cumulative live birth rates per aspiration depends on female age: a population study of 221 221 treatment cycles.

STUDY QUESTION: What is the number of oocytes where the maximum cumulative live birth rate per aspiration (CLBR) is observed during ART in women of different ages? SUMMARY ANSWER: The maximum CLBR was observed when around 25 oocytes were retrieved in women between 18-35 years of age, around 9 oocytes in women more than 45 years of age and continued to increase beyond 30 oocytes in women between 36-44 years of age. WHAT IS KNOWN ALREADY: The live birth rate per fresh or frozen/thaw embryo transfer (FET) procedure has traditionally been the main measure of ART success. However, with the introduction of highly efficient embryo cryopreservation methods, CLBR encompassing live delivery outcomes from the fresh and all subsequent FET following a single ovarian stimulation and oocyte collection is increasingly viewed as a more meaningful measure of treatment success. There is evidence suggesting that larger oocyte yields are associated with increased likelihood of cumulative live birth per aspiration. Whether this association is the same across female ages has not yet been properly investigated. STUDY DESIGN, SIZE, DURATION: This is a large retrospective population-based cohort study using data from the Australian and New Zealand Assisted Reproduction Database (ANZARD). ANZARD contains information from all ART treatment cycles carried out in all fertility centres in Australia and New Zealand. Overall, 221 221 autologous oocyte aspiration cycles carried out between January 2009 to December 2015 were included in the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cumulative live birth per aspiration was defined as at least one liveborn baby at ≥20 weeks gestation resulting from an ART aspiration cycle, including all fresh and FET resulting from the associated ovarian stimulation, until one live birth occurred or all embryos were used. Cycles where no oocytes were retrieved were excluded from analysis as there is no possibility of live birth. Analyses of data were performed using generalized estimating equations to account for the clustered nature of data (multiple cycles undertaken by a woman). Univariate and multivariable regression analysis was performed to identify and adjust for factors known to independently affect cumulative live birth per aspiration. An interaction term between female age and the number of oocytes retrieved was included to assess whether the age of the women was associated with a different optimal number of oocytes to achieve at least one live birth from an aspiration cycle (i.e. the effect-modifying role of female age). The likelihood of cumulative live birth per aspiration was calculated as odds ratios (ORs) with 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE: The median number of oocytes retrieved was 7 (interquartile range, 4-12) and median age of patients was 36 (interquartile range, 33-40). The overall CLBR was 32.2%. The results from the multivariable regression analysis showedthat the number of oocytes retrieved remained a significant predictor (P < 0.001) of cumulative live birth per aspiration after adjusting for female age, parity and cycle count. Compared to the reference group of 10-14 oocytes retrieved, the adjusted odds for cumulative live birth per aspiration increased with the number of oocytes retrieved: 1-3 oocytes, 0.21 (95% CI, 0.20-0.22); 4-9 oocytes, 0.56 (95% CI, 0.55-0.58); 15-19 oocytes, 1.38 (95% CI, 1.34-1.43); 20-24 oocytes, 1.75 (95% CI, 1.67-1.84); and 2.10 (95% CI, 1.96-2.25) with more than 25 oocytes. After stratifying by female age group, the rate of increase in CLBR per additional oocyte retrieved was lower in the older age groups, indicating that higher oocyte yields were more beneficial in younger women. CLBR of patients in the <30 years and 30-34 years age groups appeared to reach a plateau (with only minimal increase in CLBR per additional oocyte retrieved) after retrieval of 25 oocytes at 73% and 72%, respectively, while CLBR of patients in the 35-39 years and 40-44 years age groups continued to increase with higher oocyte yields, reaching 68% and 40%, respectively, when 30 or more oocytes were retrieved. CLBR of patients aged 45 years and above remained consistently below 5%. Findings suggest that the number of oocytes retrieved where CLBR appears to be maximized is around 25 in women between 18-35 years, more than 30 in women between 36-44 years and around 9 in women 45 years and older. However, results for women aged 45 years and older may not be as robust due to the relatively small sample size available in this age group. LIMITATIONS, REASONS FOR CAUTION: As with all large retrospective database studies, there are potential confounders that cannot be accounted for. Despite the current study being based on complete ascertainment of ART cycles across two countries, ovarian stimulation protocols, oocyte quality parameters and a number of important patient characteristics are not collected by ANZARD. Additionally, a small number of cycles were available for women over 45 years yielding more than 15 oocytes, making these estimates unreliable. WIDER IMPLICATIONS OF THE FINDINGS: The results from this study demonstrate that the number of oocytes retrieved where the maximum CLBR is observed during ART is dependent on female age. This provides information for clinicians and patients to understand the modifying effect of age on the number of oocytes retrieved and the likelihood of success with ART. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. The Fertility Society of Australia funds the National Perinatal Epidemiology and Statistics Unit to manage ANZARD and conduct national reporting of ART in Australia and New Zealand. Associate Professor Georgina Chambers (G.C.) is employed by the University of New South Wales (UNSW) and is director of the National Perinatal Epidemiology and Statistics Unit at UNSW. G.C. was also a paid member of the Australian governments Medicare Benefits Scheme taskforce on assisted reproductive technologies in 2017.

In vitro fertilization healthcare professionals generally underestimate patients' satisfaction with quality of care.

INTRODUCTION: Previous studies have mainly compared professionals' and patients' ratings of the importance of different care aspects, finding poor agreement between the groups concerning patient-centered quality of care. There is still little known about professionals' knowledge of how patients experience the quality of care they receive during in vitro fertilization (IVF) treatments. The aim of this study was to investigate how IVF healthcare professionals estimate patients' experience of patient-centered quality of care and if certain factors influenced the IVF professionals' perceptions and IVF patients' experience of quality of care. MATERIAL AND METHODS: All 16 IVF public and private clinics in Sweden participated in this cross-sectional study. A total of 268 IVF healthcare professionals and 3298 patients (women and men) undergoing IVF treatment between January and May 2015 participated by answering the validated questionnaire "Quality from the patients' perspective of in vitro fertilization treatment" (QPP-IVF). RESULTS: Healthcare professionals significantly underestimated patients' satisfaction with the patient-centered quality of care they received in all aspects measured. Both patients and professionals rated the most deficient factors to be "responsibility/continuity", "participation" and "availability". Healthcare professionals and patients belonging to private clinics evaluated patient-centered care as significantly better than professionals and patients at public clinics in almost all aspects measured. CONCLUSION: The results of this study will increase the professionals' understanding of the patients' experiences during IVF treatment and provide additional knowledge when identifying areas to prioritize to improve quality of care.

Women's adjustment trajectories during IVF and impact on mental health 11-17 years later.

STUDY QUESTION: Do patients present different adjustment trajectories during and after IVF treatment? SUMMARY ANSWER: Most women show resilient trajectories during and after IVF treatment but 37% show temporary or chronic maladjustment during IVF and 10% are maladjusted 11-17 years after treatment. WHAT IS KNOWN ALREADY: Research on patient psychosocial adjustment during treatment has contributed to identifying the most distressful stages of IVF treatment and profiling patients at risk for emotional maladjustment at these specific stages. This knowledge is currently driving the deliverance of psychosocial care at fertility clinics by tailoring it to patients' risk profiles and specific treatment stages. However, current care does not take into consideration how individuals adjust across the entire treatment pathway. This can be assessed by profiling individual adjustment trajectories. STUDY DESIGN, SIZE, DURATION: A longitudinal cohort study with five assessment moments that combines data from two different studies, the STRESSIVF and OMEGA projects. Participants enrolled in the STRESSIVF study (started IVF in 1998-2000) were assessed before and after the first IVF treatment cycle and 6 months and 2.5 years after the last IVF cycle. A subset participated in the OMEGA project (started IVF in 1995-2000) and reported on their mental health 11-17 years after treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three hundred and forty-eight women participated in the STRESSIVF project and 108 of these in the OMEGA. Anxiety was measured with the State and Trait Anxiety Inventory, depression with the Beck Depression Inventory and mental health with the Mental Health Inventory. Latent class growth mixed modelling was carried out to identify distinct anxiety and depression trajectories over the four STRESSIVF study assessment moments. Multinominal logistic regressions were conducted to investigate predictors of trajectory membership, and stepwise linear regressions were performed to investigate if adjustment trajectories predicted mental health 11-17 years after IVF treatment. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 67 and 86% of women showed normal levels of anxiety and depression, respectively, throughout treatment (resilient trajectories), 24 and 33% experienced anxiety and depression only during treatment (recovery trajectories), 4.6 and 4.9% experienced anxiety and depression only after treatment (delayed trajectories), and 4.3% showed chronic anxiety (chronic trajectory, not identified for depression). Non-resilient trajectories were associated with unsuccessful treatment, marital dissatisfaction, lack of social support and negative infertility cognitions. One in 10 women had a delayed or chronic trajectory and these trajectories predicted serious mental health impairment 11-17 years after treatment. LIMITATIONS, REASONS FOR CAUTION: The study only focuses on women. In the OMEGA project adjustment was assessed using a mental health measure. Although we could investigate how trajectories predicted mental health, it would have been preferable to map anxiety and depression trajectories up to 11-17 years after treatment. Missing analysis showed selective dropout from the study but this was accounted for by using mixed models and imputation procedures. Finally, data on other life stressors were not collected; therefore any contribution from these events cannot be assessed. WIDER IMPLICATIONS OF THE FINDINGS: Fertility health-care providers have been called upon considering their responsibility in supporting patients in the aftermath of treatment. Results show it is possible to profile different groups of at-risk women at the start of the treatment and tailor psychosocial support to risk profile to promote health adjustment during treatment and thereafter. STUDY FUNDING/COMPETING INTERESTS: This study was supported by a grant from the Dutch Cancer Society (2006-3631) and the Praeventiefonds (28-3012). No competing interests exist.

Serum uric acid did not affect embryonic and pregnancy outcomes in women without PCOS during IVF procedures.

Objectives: Serum uric acid (UA) levels are associated with many systemic diseases. A previous study confirmed the association between high serum uric acid levels and poor prognosis of in vitro fertilization (IVF) treatment in polycystic ovary syndrome (PCOS) patients. This study aimed to explore the correlation between serum uric acid levels and reproductive outcomes in patients without PCOS. Methods: A retrospective study that included 1057 patients who underwent pre-implantation genetic testing for monogenic disorders (PGT-M) treatment from January 2013 to December 2020 was conducted. The study population was further divided into 3 groups according to serum UA levels: the ≤250 µmol/L group, the 251-360 µmol/L group, and the >360 µmol/L group. The controlled ovarian hyperstimulation (COH) treatment outcomes, embryonic treatment outcomes and pregnancy outcomes of the first frozen embryo transfer (FET) cycle were compared among groups. Multivariable linear regression and binary regression were applied to detect the association between IVF outcomes and serum uric acid levels. Results: The number of retrieved oocytes, fertilization rate, viable embryo rate, blastocyst formation rate and euploid rate were not associated with serum uric acid levels. The mature oocyte rate was negatively correlated with serum uric acid levels. The pregnancy outcomes of the first FET cycle were also not associated with serum uric acid levels. After adjustment for BMI, the perinatal outcomes were not associated with serum uric acid levels. Conclusion: IVF treatment outcomes were not associated with serum uric acid levels in patients without PCOS.

FSH administration at 12-hour intervals for the first 2 days, combined with mandatory GnRH-agonist trigger and blastocyst vitrification in women (<80Kg) with high AMH levels, results in higher cumulative live birth rates and is safer.

We aimed to determine if a programme change to 12 hourly injections of FSH (150 IU per injection) for the first 2 days of stimulation in women with high ovarian reserve (AMH ≥ 30 pmol/L), followed by 24 hourly injections, would elicit increased earlier follicular recruitment, higher egg yields and blastocyst embryos for cryopreservation, leading to potential higher cumulative pregnancy rates, than conventional daily injections throughout. For safety reasons, the approach required mandatory cryopreservation of all blastocysts (mFET group; n = 74), after ovulation trigger with GnRH-agonist, in GnRH-antagonist controlled cycles. The 'Comparator group' (n = 91) comprised women with the same high AMH levels treated with the same base dose of FSH, with the aim of fresh blastocyst transfer and cryopreservation of supernumerary embryos, treated over the preceding 2 years. There was no difference in age, AMH, weight or BMI between the groups. The mFET group achieved higher egg (17.7 versus 11.7; p < 0.001) and embryo (10.9 versus 7.2; p < 0.001) yields and fewer cases with sub-optimal embryo yields (7% versus 22%; p = 0.018). The cumulative live birth rate was superior in the mFET group (73% versus 43%), as was the safety profile, and negligible rate of treatment plan modification.

Does in vitro fertilization (IVF) treatment provide good value for money? A cost-benefit analysis.

Background: Using traditional health technology assessment (HTA) outcome metrics, such as quality-adjusted life-years, to assess fertility treatments raises considerable methodological challenges because the objective of fertility treatments is to create new life rather than extend, save, or improve health-related quality of life. Objective: The aim of this study was to develop a novel cost-benefit framework to assess value for money of publicly funded IVF treatment; to determine the number of cost-beneficial treatment cycles for women of different ages; and to perform an incremental cost-benefit analysis from a taxpayer perspective. Methods: We developed a Markov model to determine the net monetary benefit (NMB) of IVF treatment by female age and number of cycles performed. IVF treatment outcomes were monetized using taxpayers' willingness-to-pay values derived from a discrete choice experiment (DCE). Using the current funding environment as the comparator, we performed an incremental analysis of only funding cost-beneficial cycles. Similar outputs to cost-effectiveness analyses were generated, including net-benefit acceptability curves and cost-benefit planes. We created an interactive online app to provide a detailed and transparent presentation of the results. Results: The results suggest that at least five publicly funded IVF cycles are cost-beneficial in women aged <42 years. Cost-benefit planes suggest a strong taxpayer preference for restricting funding to cost-beneficial cycles over current funding arrangements in Australia from an economic perspective. Conclusions: The provision of fertility treatment is valued highly by taxpayers. This novel cost-benefit method overcomes several challenges of conventional cost-effectiveness methods and provides an exemplar for incorporating DCE results into HTA. The results offer new evidence to inform discussions about treatment funding arrangements.

Synthetic Pyrethroids Exposure and Embryological Outcomes: A Cohort Study in Women from Fertility Clinic.

Pyrethroids exposure has been associated with adverse reproductive outcome. However, there is no study that explores the effect of environmental exposure and embryological outcomes. This question was addressed in a prospective cohort of couples undergoing fertility treatment. The study aims to assess the association between urinary metabolites of synthetic pyrethroids and embryological outcomes (MII oocyte count, top quality embryo, fertilization and implantation rate). We included 450 women aged 25−45 undergoing assisted reproductive technology (ART) cycle at Infertility Clinic in Poland. Urine samples were collected at the time of fertility procedure(s) to assess four urinary synthetic pyrethroids concentrations (3-phenoxybenzoic acid (3PBA), cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA), trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans-DCCA), cis-2,2-dibromovinyl-2,2-dimethylocyclopropane-1-carboxylic acid (DBCA)) using validated gas chromatography ion-tap mass spectrometry and calculated for each cycle-specific metabolite. To evaluate the effect of environmental exposure to synthetic pyrethroids and embryological outcomes (methaphase II (MII) oocyte yield, top quality embryo, fertilization rate, implantation rate), multivariable generalized linear mixed analyses with random intercepts were prepared. Urinary 3-PBA concentrations decrease MII oocyte count (p = 0.007) in the fourth quartile (>75 percentile) compared to women in the first quartile (≤25 percentile). Additionally, when 3-PBA was treated as continuous variable, the negative association between exposure to pyrethroids and MII oocyte count was also observed (p = 0.012). Exposure to other pyrethroid metabolities (CDCCA, TDCCA, DBCA) was not related to any of the examined embryological outcomes. Exposure to synthetic pyrethroids may be associated with poorer embryological outcome among couples seeking fertility treatments. As this is the first study on this topic, the results need to be confirmed in further studies.

Endometrial Liquid Biopsy Provides a miRNA Roadmap of the Secretory Phase of the Human Endometrium.

CONTEXT: Endometrial liquid biopsy (ELB) is a minimally invasive alternative for research and diagnosis in endometrial biology. OBJECTIVE: We sought to establish an endometrial micro ribonucleic acid (miRNA) roadmap based on ELB during the secretory phase of the menstrual cycle in both natural and hormonal replacement therapy (HRT) cycles. DESIGN: Human ELB samples (n = 58) were obtained from healthy ovum donors undergoing a natural and an HRT cycle consecutively. miRNA profiles were identified using next-generation sequencing (NGS). For functional analysis, messenger ribonucleic acid targets were chosen among those reported in the endometrial receptivity analysis. RESULTS: The human endometrial secretory phase is characterized by a dynamic miRNA secretion pattern that varies from the prereceptive to the receptive stages. No differences in miRNA profiles were found among natural versus HRT cycles in the same women, reinforcing the similarities in functional and clinical outcomes in natural versus medicated cycles. Bioinformatic analysis revealed 62 validated interactions and 81 predicted interactions of miRNAs differentially expressed in the HRT cycle. Annotation of these genes linked them to 51 different pathways involved in endometrial receptivity. CONCLUSION: This NGS-based study describes the miRNA signature in human ELB during the secretory phase of natural and HRT cycles. A consistent endometrial miRNA signature was observed in the acquisition of endometrial receptivity. Interestingly, no significant differences in miRNA expression were found in natural versus HRT cycles reinforcing the functional clinical similarities between both approaches.

Failure after fertility treatment: regulation strategies when facing a blocked parenthood goal.

Biological parenthood is a central life-goal for many couples that can become blocked when they experience infertility. Many couples who undergo fertility treatment will face failure and consequently have to decide whether to continue with treatment. The present study used the qualitative methodology of Interpretative Phenomenological Analysis to examine self-regulatory approaches that underlie decision-making about continuing treatment. One-time, one-on-one, semi-structured, in-depth interviews were conducted with 16 individuals (eight heterosexual couples) after they had experienced at least one treatment failure and were considering whether to undergo another treatment. After treatment failure, individuals used several approaches to remain engaged with biological parenthood, including reframing treatment failure as a learning tool and emphasizing the importance of persistence in achieving success. The apparent decision to continue with treatment was considered non-negotiable and largely made by women in the partnership. Once the decision was made to pursue treatment, it was not discussed further. Given individuals' willingness to engage in treatment, patients should be offered additional support to consider wide psychosocial implications of continuing treatment.

Pre-Conception Interventions for Subfertile Couples Undergoing Assisted Reproductive Technology Treatment: Modeling Analysis.

BACKGROUND: Approximately 1 in 7 couples experience subfertility, many of whom have lifestyles that negatively affect fertility, such as poor nutrition, low physical activity, obesity, smoking, or alcohol consumption. Reducing lifestyle risk factors prior to pregnancy or assisted reproductive technology treatment contributes to the improvement of reproductive health, but cost-implications are unknown. OBJECTIVE: The goal of this study was to evaluate reproductive, maternal pregnancy, and birth outcomes, as well as the costs of pre-conception lifestyle intervention programs in subfertile couples and obese women undergoing assisted reproductive technology. METHODS: Using a hypothetical model based on quantitative parameters from published literature and expert opinion, we evaluated the following lifestyle intervention programs: (1) Smarter Pregnancy, an online tool; (2) LIFEstyle, which provides outpatient support for obese women; (3) concurrent use of both Smarter Pregnancy and LIFEstyle for obese women; (4) smoking cessation in men; and (5) a mindfulness mental health support program using group therapy sessions. The model population was based on data from the Netherlands. RESULTS: All model-based analyses of the lifestyle interventions showed a reduction in the number of in vitro fertilization, intracytoplasmic sperm injection, or intrauterine insemination treatments required to achieve pregnancy and successful birth for couples in the Netherlands. Smarter Pregnancy was modeled to have the largest increase in spontaneous pregnancy rate (13.0%) and the largest absolute reduction in potential assisted reproductive technology treatments. Among obese subfertile women, LIFEstyle was modeled to show a reduction in the occurrence of gestational diabetes, maternal hypertensive pregnancy complications, and preterm births by 4.4%, 3.8%, and 3.0%, respectively, per couple. Modeled cost savings per couple per year were €41 (US $48.66), €360 (US $427.23), €513 (US $608.80), €586 (US $695.43), and €1163 (US $1380.18) for smoking cessation, mindfulness, Smarter Pregnancy, combined Smarter Pregnancy AND LIFEstyle, and LIFEstyle interventions, respectively. CONCLUSIONS: Although we modeled the potential impact on reproductive outcomes and costs of fertility treatment rather than collecting real-world data, our model suggests that of the lifestyle interventions for encouraging healthier behaviors, all are likely to be cost effective and appear to have positive effects on reproductive, maternal pregnancy, and birth outcomes. Further real-world data are required to determine the cost-effectiveness of pre-conception lifestyle interventions, including mobile apps and web-based tools that help improve lifestyle, and their effects on reproductive health. We believe that further implementation of the lifestyle app Smarter Pregnancy designed for subfertile couples seeking assistance to become pregnant is likely to be cost-effective and would allow reproductive health outcomes to be collected.