Unsuccessful Cycles Research Articles

Do women with severely diminished ovarian reserve undergoing modified natural-cycle in-vitro fertilization benefit from earlier trigger at smaller follicle size?

To evaluate whether trigger and oocyte collection at a smaller follicle size decreases the risk of premature ovulation while maintaining the reproductive potential of oocytes in women with a severely diminished ovarian reserve undergoing modified natural-cycle in-vitro fertilization. This was a retrospective cohort study including women who had at least one unsuccessful cycle (due to no response) of conventional ovarian stimulation with a high dosage of gonadotropins and subsequently underwent a modified natural cycle with a solitary growing follicle (i.e. only one follicle > 10 mm at the time of trigger). The association between follicle size at trigger and various cycle outcomes was tested using regression analyses. A total of 160 ovarian stimulation cycles from 110 patients were included in the analysis. Oocyte pick-up (OPU) was performed in 153 cycles and 7 cycles were canceled due to premature ovulation. Patients who received their trigger at smaller follicle sizes (≤ 15 mm) had significantly lower rates of premature ovulation and thus higher rates of OPU (98.9% vs 90.8%; odds ratio, 9.56 (95% CI, 1.58-182.9); P = 0.039) compared with those who received their trigger at larger follicle sizes (> 15 mm). On multivariable analysis, smaller follicle sizes at trigger (> 10 to 13 mm, > 13 to 15 mm, > 15 mm to 17 mm) were not associated significantly with a lower rate of cumulus-oocyte complex (COC) retrieval, metaphase-II (MII) oocytes or blastulation when compared to the > 17-mm group. On sensitivity analysis including only the first cycle of each couple, the maturity rate among those with COC retrieval was highest in follicle sizes > 15 to 17 mm (92.3%) and > 13 to 15 mm (91.7%), followed by > 10 to 13 mm (85.7%) and lowest in the > 17-mm group (58.8%). During the study period, five euploid blastocysts developed from 48 fertilized MII oocytes with follicle sizes of 12 mm (n = 3), 14 mm (n = 1) and 16 mm (n = 1) at trigger. Of those, four were transferred and resulted in two live births, both of which developed from follicles with a size at trigger of 12 mm. The ideal follicle size for triggering oocyte maturation may be smaller in women with a severely diminished ovarian reserve managed on a modified natural cycle when compared to conventional cut-offs. The risk of OPU cancellation was significantly higher in women triggered at follicle size > 15 mm and the yield of mature oocytes was not adversely affected in women triggered at follicle size > 13 to 15 mm compared with > 15 to 17 mm. Waiting for follicles to reach sizes > 17mm may be detrimental to achieving optimal outcome. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

O-080 The effect of psychosocial support on motivation for assisted reproductive treatments

Abstract Study question Does psychosocial intervention targeting better psychological adjustment increase the likelihood of treatment continuation among women pursuing assisted reproductive technologies (ART)? Summary answer After a psychosocial intervention, a robust amelioration occurred in distress levels, yet no notable change was detected in motivational levels for treatment continuation. What is known already Approximately 20% of patients stop ART treatments prematurely, often after three unsuccessful cycles, even in countries with a public funding of ART, despite a 15% success rate increase per recommended cycle. Emotional distress, poor prognosis, and financial burden are risk factors for early cessation. Since depression has been shown to predict ART discontinuation, it is logical to expect that an alleviation of depression is accompanied by a strengthening of the intention for treatment continuation. Study design, size, duration A prospective, pre-post design, single-centre, interventional cohort study was performed between December, 2019 and October, 2022 (start and end of recruitment, respectively). 2636 patients were approached for study purposes, 610 were assessed for eligibility, and 168 were included in the intervention. With a 8.3% attrition rate, data of 154 patients were analysed in this study, originally a randomized controlled trial, whose data were pooled for the present purposes. Participants/materials, setting, methods Women scoring in mild-to-moderate impairment ranges on four psychological tests were invited to take part in a 10-week, 135-minute/week intervention at the assisted reproduction centre of a large university hospital. Psychological data were collected pre- and post-intervention, alongside demographic and fertility specifics. Perceived probability of treatment continuation in the event of an unsuccessful ART cycle was assessed with a Likert-scale single question at both time points. Multivariate linear models were utilized for statistical analysis. Main results and the role of chance In comparison with baseline values, significant changes in the expected direction occurred in depressive symptoms, anxiety values, infertility-specific stress and fertility-related quality of life (t-values ranging from 6.559 to 7.949; all p-values<0.001). However, neither treatment-related quality of life (t = 0.718; p = 0.474), nor motivational levels for treatment continuation changed significantly (t = 1.058; p = 0.292). Age, however, had a significant main effect on perceived probability of treatment continuation (t = 2.864; p = 0.004). Limitations, reasons for caution Limitations include potential inter-group differences, unmeasured motivational factors, and no male partner data. Biological factors other than age, aetiology and duration of infertility may have confounded study results. Another limitation is the lack of long-term follow-up, given that perceived probability of treatment continuation may not coincide with actual behaviour. Wider implications of the findings Psychosocial interventions are efficient in alleviating distress but these improvements may not directly impact motivational changes. Biological factors such as age may have a more accentuated effect on ART treatment continuation than psychological aspects. Alternative hypotheses on precise determinants and modifiable factors influencing motivation need testing. Trial registration number Not applicable

Testicular sperm retrieval for intracytoplasmic sperm injection: when to consider it after unsuccessful intracytoplasmic sperm injection with ejaculated sperm?

The question of whether patients are more likely to succeed with testicular sperm intracytoplasmic sperm injection (T-ICSI) after unsuccessful ICSI with ejaculated sperm (Ej-ICSI) remains unknown. The study aimed to identify potential predictors of successful T-ICSI in men with idiopathic infertility and oligozoospermia (sperm concentration<15 × 106/mL, non-azoospermic) who had previously experienced unsuccessful Ej-ICSI. In total, 154 couples with male partners who had oligozoospermic conditions after two unsuccessful cycles of Ej-ICSI switched to T-ICSI. Before initiating T-ICSI, the sperm DNA fragmentation index (DFI) was assessed in ejaculated specimens. Participants were divided into two groups: group A (live birth (+), n=60) and group B (live birth (-), n=94). Fertilization, clinical pregnancy, live births, and miscarriages had rates of 72.7%, 44.2%, 39%, and 5.2%, respectively. The total motile sperm (TMS) count in group A was significantly higher (3.8±1.5 million) than in group B (3±1.6 million; p=0.002). DFI was significantly higher in group A (24.2±12.3) than in group B (18.1±11; p=0.001). Hormone levels and oocyte counts showed no statistically significant differences between groups. Multivariate regression analysis revealed that TMS (odds ratio [OR]: 1.46; 95% CI, 1.14-1.87, p=0.003) and DFI (OR: 1.04; 95% CI, 1.01-1.08, p=0.009) were found to be significant predictors of live birth outcomes. At a cutoff point of 2.55 (area under the curve [AUC]=0.65), the optimal sensitivity and specificity values for TMS were 78% and 48%, respectively. At a cutoff point of 25.8 (AUC=0.65), DFI had a maximum sensitivity of 51.7% and a specificity of 78.7%. TMS and DFI were found to be significant predictors of live birth outcomes in couples with oligozoospermic male partners undergoing T-ICSI. These findings may help clinicians tailor treatment strategies for this specific patient population.

Artificial intelligence-powered assisted ranking of sibling embryos to increase first cycle pregnancy rate

Research questionCould EMBRYOLY, an artificial intelligence embryo evaluation tool, assist embryologists to increase first cycle pregnancy rate and reduce cycles to pregnancy for patients? DesignData from 11,988 embryos were collected via EMBRYOLY from 2666 egg retrievals (2019–2022) across 11 centres in France, Spain and Morocco using three time-lapse systems (TLS). Data from two independent clinics were also examined. EMBRYOLY's transformer-based model was applied to transferred embryos to evaluate ranking performances against pregnancy and birth outcomes. It was applied to cohorts to rank sibling embryos (including non-transferred) according to their likelihood of clinical pregnancy and to compute the agreement with the embryologist's highest ranked embryo. Its effect on time to pregnancy and first cycle pregnancy rate was evaluated on cohorts with multiple single blastocyst transfers, assuming the embryologist would have considered EMBRYOLY's ranking on the embryos favoured for transfer. ResultsEMBRYOLY's score correlated significantly with clinical pregnancies and live births for cleavage and blastocyst transfers. This held true for clinical pregnancies from blastocyst transfers in two independent clinics. In cases of multiple single embryo transfers, embryologists achieved a 19.8% first cycle pregnancy rate, which could have been improved to 44.1% with the adjunctive use of EMBRYOLY (McNemar's test: P < 0.001). This could have reduced cycles to clinical pregnancy from 2.01 to 1.66 (Wilcoxon test: P < 0.001). ConclusionsEMBRYOLY's potential to enhance first cycle pregnancy rates when combined with embryologists' expertise is highlighted. It reduces the number of unsuccessful cycles for patients across TLS and IVF centres.

Factors Affecting the Outcomes of First in vitro Fertilization and Embryo Transfer: A Retrospective Investigation.

The outcome of embryo transfer (ET) is multifactorial. A variety of patient-related, procedural-related, and operator-related factors are known to play a role. This study aims to evaluate the outcomes of ET and determine the factors that affect the outcome. The study involved a retrospective design involving 300 first in vitro fertilization and embryo transfer (IVF-ET) cycles between 2011 and 2021. The outcome included 155 unsuccessful cycles and 145 successful IVF-ET leading to pregnancy. The outcomes were examined for different variables, including age, weight, height, body mass index, cause of infertility, number of embryos fertilized during the cycle, day of ET, whether the embryo was frozen, presence of blood or mucus during the procedure, the use of a stylet, tenaculum, uterine sound/dilator, and catheter type. Logistic regression was used to analyze factors affecting the outcomes of ET. The mean age was 27.84 ± 3.77 years. Patients who had blood during the procedure (32.9% vs 17.2%, p = 0.002), mucus (31% vs 20.7%, p = 0.049), or used the tenaculum (16.8% vs 6.9%, p = 0.012) were more likely to have unsuccessful IVF-ET.Logistic regression to adjust for related factors revealed that the presence of blood (AOR = 2.21, 95% CI 1.04 to 4.66, p = 0.038) during the ET had a higher likelihood of an unsuccessful outcome. This study showed that the presence of blood during the ET cycle influenced clinical pregnancy. This highlights the importance of performing the procedure under atraumatic conditions. Level III; retrospective comparative study.

BG02 A case of Werner syndrome: undiagnosed progeroid syndrome presenting as female pattern hair loss

Abstract A 27-year-old woman of Pakistani heritage with a background of type 2 diabetes, hypertension, hypothyroidism, infertility and Achilles tendinopathy was referred to the dermatology department for diffuse hair loss. She had greying of the scalp hair from the age of 20 years and, on examination, there were signs of hair fragility and thinning. Biopsies showed female pattern hair loss. Topical minoxidil 5% twice daily was advised. At the consultation, it was noted that her facial features included a thin nose with micrognathia. She had dental implants and had undergone cataract surgery at 19 years of age. Scleroderma-like changes were noted on the face and over the distal joints, alongside axillary freckling and excessive lentigines for her age and skin type. She was of short stature and low weight, with a body mass index (BMI) of 15.4 kg m–2. There was thenar and hypothenar wasting and loss of gluteal fat. Her parents were consanguineous (first cousins). One of her brothers, who had similar facial features, died aged 30 years from osteosarcoma. The patient and her partner had undergone two unsuccessful cycles of in vitro fertilization following 5 years of failure to conceive naturally. Medication consisted of atorvastatin, Calcichew, levothyroxine, lisinopril, metformin, pioglitazone and repaglinide. Routine bloods and hormone profile were normal. Despite her age, BMI and statin treatment, blood lipids were raised and a liver ultrasound showed fatty changes. The dermatology department queried Werner syndrome and referral to a tertiary lipodystrophy clinic was made. The lipodystrophy genetic panel was completed. Homozygous null mutation at the WRN locus was found confirming a diagnosis of Werner syndrome. Werner syndrome is an extremely rare autosomal recessive form of progeroid syndrome first described by Otto Werner in 1904. The hallmark sign is the striking disproportion between the patient’s age and appearance. WRN encodes the eponymous WRN protein, a member of the RecQ-like DNA helicase family. The prognosis is unfavourable, with a mean survival of 54 years. Primary causes of mortality are cardiovascular disease and malignancy, with melanoma, thyroid cancer, osteosarcoma and soft tissue sarcoma being the most common forms. There is currently no specific treatment. Management is close multidisciplinary monitoring and treatment of associated conditions. A 2010 study of the Werner syndrome mouse model found vitamin C supplementation to be beneficial (Massip L, Garand C, Paquet ER et al. Vitamin C restores healthy aging in a mouse model for Werner syndrome. FASEB J 2010; 24:158–72). As the condition results in excess damage on ultraviolet exposure and a high risk of melanoma, as well as nonmelanoma skin cancers, an annual dermatology skin check is required.

P-292 It is feasible to carry out a large-scale multi-national Assisted Reproductive Technology Real World Data (RWD) collection prospectively, encompassing collected patient and treatment cycle information

Abstract Study question Is it feasible to carry out a large-scale multi-national Assisted Reproductive Technology Real World Data (RWD) collection prospectively, encompassing collected patient and treatment cycle information? Summary answer The creation of an international database collecting RWD is feasible. The quality and quantity of the data allow them to be used for research purposes. What is known already Real World Evidence (RWE) may help to answer clinical research questions that are relevant to a broad population of patients. For 40 years, Assisted Reproductive Technology (ART) treatment cycle data have been collected in national registries. The aggregated national data are further collated on an international level. These data are useful for describing secular trends in ART utilization and associated outcomes. However, registries often fall short in providing patient-level and treatment-cycle-level information for data collation and analysis. Furthermore, national registries may restrict access of raw data for open research, for political, infrastructural, or legal reasons. Study design, size, duration In a first phase, the OPERA database (Observational retrospective ProjEct for a Research database for ART procedures) included data from cycles recorded between January 2016 and December 2020 in eighteen clinics, providing a robust sample size for Real World Data analyses. Fondazione per la Ricerca Ospedale di Bergamo (FROM), together with expert clinicians in the ART field, promoted the OPERA project with the financial support from two pharmaceutical companies (Merck KGaA, IBSA SA). Participants/materials, setting, methods The Eighteen clinics located in Germany and Italy joining the OPERA data collection, have proven expertise in ART procedures and use MedITEX® DB. The study protocol was reviewed by the competent Ethic Committees and Data Protection Officers. Among the outcomes collected were the mean number of cycles, the pregnancy and birth rate per Embryo Transfer, and the pregnancy and birth rates as a function of female age. The first extraction was scheduled for December 2022. Main results and the role of chance Around 75,000 ART cycles were collected from the first ten participating centers. Among the around 45,000 cycles that have available fertilization information , 11,553 (25.7%) were the In-Vitro Fertilization treatments (IVF), 31,202 (69.3%) Intracytoplasmic Sperm Injection treatments (ICSI), and 2,282 (5.1%) a combination of the two techniques. Of the adopted stimulation protocols, 38.43% (10,538) of the total were with variable antagonists, 31.27% (8,574) were with a single antagonist, 24.31% (6,665) were with a long agonist, 5.51% (1,511) were with a short agonist, and 0.35% (96) were with fixed antagonists. The average number of oocytes retrieved is 11.28, with a median of 10.0. The average number of 2 Pronuclear Oocytes (2PN) obtained is 3.7, with a median of 3.0. Moreover, the average number of 8 cell embryos at day 3 is 2.0, with a median of 2.0. It was also recorded the rate of unsuccessful cycles with no oocytes retrieved (4.8%). Among the cycles collected, 2.9% of the total were from frozen oocytes. Most of the ET (40.0%) were performed 5 days after the oocyte retrieval. Limitations, reasons for caution Amassing ART cycle information does not compensate for the well-known insufficiencies of primary data quality, of information on confounders and of access to patient level data. Moreover, the technical risk of this project is the potential loss of participant confidentiality, mitigated through a full anonymization. Wider implications of the findings The OPERA project may facilitate the transition of ART surveillance from a national aggregate level to a large-scale individual patient and treatment cycle level. Furthermore, as an evolutionary path, the OPERA project may help building large and longitudinal databases, suitable for appropriate epidemiological research in ART. Trial registration number not applicable

P-592 Follicular GnRH agonist challenge test (FACT) to predict suboptimal response to GnRH agonist trigger in oocyte cryopreservation cycles

Abstract Study question Can follicular GnRH agonist administration predict suboptimal response to GnRH agonist trigger assessed by LH levels post ovulation trigger in non-medical oocyte cryopreservation program? Summary answer Follicular agonist challenge test (FACT) can serve as an adjunct pre-trigger, intracycle tool to predict adequate response to agonist trigger. What is known already Suboptimal response to GnRH agonist ovulation trigger refers to failure to retrieve the expected number of oocytes. It was demonstrated in up to 5.5% of cycles based on relatively low number of studies with heterogenous suboptimal response definitions and prevalence, no clear cut-offs and mainly post - stimulation tools to predict unsuccessful cycle. The most studied variable associated with suboptimal response was LH levels 10-12 hours after ovulation trigger below 12-15IU. Study design, size, duration We prospectively recruited all women that underwent non-medical fertility preservation in our tertiary university affiliated medical center between October 2020 and February 2022 and agreed to participate in the study. The study included 91 women. Participants/materials, setting, methods On day 2 to menstrual cycle, blood tests were drawn (basal Estradiol/E2, basal FSH/FSH2, basal LH/LH2, Progesterone/P2) and ultrasound (US) was performed. On that evening, the women were instructed to inject 0.2 mg GnRH agonist and arrive for repeated blood workup 10-12 hours later at the next morning, followed by a flexible antagonist protocol. On the morning after ovulation trigger blood tests were again taken and LH levels were compared to FACT LH levels. Main results and the role of chance LH levels following agonist ovulation trigger below 15IU occurred in 1.09 % of cycles and were predicted by FACT, r = 0.57, p &amp;lt; 0.001. ROC analysis demonstrated that FACT LH &amp;gt; 42.70 IU would predict LH post trigger of more than 30 IU with 75% sensitivity and 70% specificity, AUC= 0.81. LH levels post trigger also displayed significant positive correlation to basal FSH (r = 0.35, p = 0.002) and basal LH (r = 0.54, p &amp;lt; 0.001). LH levels post ovulation trigger were not associated with total oocytes number or maturity rate. The strongest correlation to the total number of retrieved oocytes and mature oocytes was progesterone level post ovulation trigger (r = 0.74, p &amp;lt; 0.001). Limitations, reasons for caution Limitation of our study include the relatively small sample size designed to detect 5% suboptimal proportion and might have been insufficient to allow identification of very rare suboptimal responses Wider implications of the findings Suboptimal response to agonist trigger, as assessed with post trigger LH levels is a rare event. FACT could serve as an adjunct pre-trigger, intracycle tool to predict adequate response to agonist ovulation trigger. Future studies should focus on optimization of agonist trigger efficacy assessment and prediction, especially in high responders. Trial registration number 0304-20-ASF

Discussing the possibility of fertility treatment being unsuccessful as part of routine care offered at clinics: patients' experiences, willingness, and preferences.

Discussing the possibility of fertility treatment being unsuccessful as part of routine care offered at clinics: patients' experiences, willingness, and preferences.

A supportive randomized clinical trial on Iranian infertile women with the history of infertility treatments dropout following unsuccessful ART cycle/s: A study protocol

IntroductionDue to high dropout rate of infertility treatments and lack of any intervention for motivating infertile couples to continue treatments, the present study will be conducted with the aim of designing, implementing and determining the effectiveness of the proposed intervention in order to continue infertility treatments. Methods& Analysis: We will conduct this study in two stages; a review of literature and past studies will be done to identify interventions that have been performed for infertile couples, and then an appropriate intervention with the aim of continuing infertility treatments for infertile women will be designed. After that a Delphi study will be designed in accordance with collected information of previous stages and will be approved by experts. In the second stage we will implement designed intervention of a randomized clinical trial on two groups of infertile women (control and intervention) with the history of infertility treatment dropout following unsuccessful cycle. We will use descriptive statistic in first and second stage. In second stage Chi square test and independent samples T test will be used to compare variables between groups and variables in study questionnaires before and after the intervention between two groups of study. DiscussionThe present study will be the first study to be performed as a clinical trial on infertile women who have discontinued the treatments, with the aim of continuing treatments. Thereupon, it seems that the results of this study will be the basis for studies around the world to prevent premature cessation of infertility treatments.

Qualitative evaluation of the acceptability and feasibility among healthcare professionals and patients of an ART multi-cycle treatment planning and continuation intervention prototype.

Is it possible to design an ART Treatment Planning and Continuation Intervention (TPCI) that is considered acceptable and feasible to patients and healthcare professionals (HCPs)? HCPs and patients responded positively to the TPCI prototype and perceived it as an acceptable intervention to support patients to stay engaged with planned treatment, but some concerns were raised about the feasibility of using it in practice. People discontinue ART due to its psychological burden. Digital tools to support people undergoing ART are available but typically focus only on practical support rather than psychological support. Research about treatment continuation and multi-cycle planning indicates that cognitive factors (expectations, intentions, efficacy beliefs) should be targets of interventions designed to help patients engage with and continue treatment to meet their personal treatment plans and goals. However, it is not known whether this form of psychological support would be acceptable for HCPs and patients or feasible to implement in practice. Qualitative cognitive interviews with HCPs and patients (May 2021). Patients were eligible if they had had a consultation to start a first/repeat stimulated IVF/ICSI cycle in the 8 weeks prior to recruitment, were aged 18 or older (upper age limit of 42 years for women) and fluent in English. Eligible HCPs were those employed by a fertility clinic who were responsible for delivering treatment planning consultations to patients. HCPs and patients were asked to think aloud while being exposed to and exploring the TPCI in one-to-one online cognitive interviews. The TPCI was designed to reduce treatment discontinuation via cognitive factors namely formation and maintenance of multi-cycle ART intentions and efficiency of decision-making during treatment, and continuation of treatment after an unsuccessful cycle (when recommended). To impact cognitive factors the TPCI comprised of two components: an expectation management and reasoning checklist for HCPs to use during planning consultations (TPCI Checklist) and a multi-feature cognitive support mobile application (TPCI App) for patients to use prior to and during treatment. After participants thought aloud while being exposed to the TPCI prototype (both components) they were asked open questions concerning their perceptions of the core components and activities on eight acceptability dimensions (e.g. acceptability, demand, integration). Interviews lasted between 40 and 90 min, were recorded, transcribed verbatim and analysed using thematic analysis. Thirteen HCPs and 13 patients participated in 25 online interviews. Thematic analysis using inductive and deductive coding generated 180 codes, grouped into 22 categories and synthesized into 9 themes. The themes showed that HCPs and patients provided positive feedback about the TPCI, perceiving it as a needed, acceptable and potentially effective way to forewarn patients of the possible need for multiple cycles, to provide patients with a sense of patient-clinic collaboration and support, and to bolster treatment intentions, all of which were perceived to contribute to reduced treatment discontinuation. HCPs perceived implementation of the TPCI Checklist to be challenging in its current length due to time pressures and clinic workload. Suggestions for enhancing the TPCI Checklist and App were provided, but none required critical changes to its core components or activities. All patients were women recruited from social media websites, mainly associated with patient support groups, who may be highly committed to their fertility treatment. HCPs were predominantly from private fertility clinics. The findings suggest there is demand for digital support geared towards motivational aspects of undergoing ART. The TPCI is an acceptable support tool to meet that need according to HCPs responsible for delivering planning consultations and patients undergoing fertility treatment. Future research is needed to develop the prototype and examine the feasibility of implementation of the TPCI in clinics. This research was financially supported by Merck Serono Ltd, an affiliate of Merck KGaA, Darmstadt, Germany. 'Merck KGaA, Darmstadt, Germany reviewed the manuscript for medical accuracy only before journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors' J.B. reports personal fees from Merck KGaA, Darmstadt, Germany, Merck AB an affiliate of Merck KGaA, Darmstadt Germany, Theramex, Organon JJC, Ferring Pharmaceuticals A/S, research grant from Merck Serono Ltd, grants from ESHRE outside the submitted work and that she is co-developer of Fertility Quality of Life (FertiQoL) and MediEmo app. S.G. reports consultancy fees from TMRW Life Sciences and Ferring Pharmaceuticals A/S, speaker fees from Access Fertility, SONA-Pharm LLC, Meridiano Congress International and Gedeon Richter. C.H. declares no conflicts of interest. N/A.

O-078 The VALUE study: a qualitative semi-structured interview study of add-on use by patients, clinicians, and embryologists in the UK and Australia

Abstract Study question Why do patients, clinicians and embryologists opt to use IVF add-ons in fertility treatment? Summary answer Add-ons offer options, hope and control in a desperate situation. The perceived drivers differ between patients and professionals; however, both feel add-ons offer bespoke care. What is known already Evidence that add-ons offer clinical advantages for the outcomes of IVF is lacking or insufficient. However, they remain popular in the UK and Australia, with over three-quarters of couples opting to use them. Professionals, clinical societies, and the media have latched onto the ethical aspects of offering non-evidence-based add-ons, often provided at an additional cost to vulnerable patients. Conversely, it has also been suggested that patients are driving add-on use. The VALUE study is the first large qualitative study to include both patients and professionals that explores the drivers behind their use, and how the existing evidence is weighed up. Study design, size, duration VALUE was a multinational semi-structured interview study in the UK and Australia. The interview schedule was reached through extensive patient and public involvement. Between January and May 2021, recruitment took place via social media advertisement, email invitation from professional societies, and snowballing. A purposive sampling strategy was planned; all eligible participants (25 patients, 25 embryologists, and 24 clinicians) were interviewed via recorded teleconference. Anonymised verbatim transcripts were analysed iteratively, and themes developed inductively. Participants/materials, setting, methods Patient and professional transcripts were coded separately using the software DedooseTM Two separate thematic analyses followed. An inductive approach to analysis was adopted, whereby themes emerged from the data, opposed to constructing a pre-conceived coding scheme. Codes were combined into broader themes, and sub-themes, which were discussed, debated, and named. The wider research team then commented upon and debated the themes and sub-themes, which were settled upon by consensus. Main results and the role of chance Thematic analysis of patient interviews identified five themes: ‘vulnerability’; ‘power of the trusted professional opinion’; ‘role of previous experience’; ‘acceptability of add-on’; and ‘the evidence doesn’t apply to me’. The professional interviews identified five themes: ‘Treating desperation’; ‘tensions within evidence-based practice’; ‘success, not profits’; ‘the patient shopper’; and ‘potential for harm’. Analysis identified that that people undergoing IVF are vulnerable and opting for non-evidence-based treatments at additional cost because of a sense of desperation following unsuccessful cycles. For patients, utilising add-ons lends hope and a sense of control, with considerations of safety and efficacy being ranked lower than hope. For professionals, add-ons are reasonable given the absence of anything else to add, and allows patients the opportunity to exhaust every avenue. At odds with one-another are the themes regarding who is driving add-on use. Patients describe the power of a professional recommendation, believing it to be in their best interest. For professionals, it’s the patients who research and request add-ons, and failing to offer them risks losing patients. The tension between evidence and bespoke care was evident across both analyses, with testimonies being particularly powerful for patients, and for professionals, a belief that add-ons are helpful in the right context. Limitations, reasons for caution The VALUE study has captured patients and professionals who have volunteered to talk about this particularly contentious area of medicine. Participants are likely to be a motivated group of individuals who may potentially represent those with strong views regarding add-ons. Wider implications of the findings The theme of desperation runs through VALUE’s analyses and whilst we did find that patients drive add-on use, professional opinion for or against add-ons was powerful. Patients want autonomy, but only in the context of informed consent. Trial registration number https://osf.io/he7tn/

O-090 Patients’ willingness and preferences about being counselled for the possibility of fertility treatment being unsuccessful

Abstract Study question What are the factors associated with patients’ willingness to be counselled about the possibility of treatment being unsuccessful and their preferences towards it? Summary answer Nine in ten patients are willing to be counselled, with willingness being associated with stronger positive attitudes towards counselling, higher perceived benefit and lower barriers What is known already Around 57% of patients in the UK end all cycles of IVF/ICSI without having a live birth. Counselling patients on this outcome could reduce the psychosocial distress they experience when it actually happens and facilitate adjustment. Patients perceive they do not have opportunity to discuss the end of treatment with staff. Staff express concerns about such counselling ‘crushing patients’ optimism’ and compromising their engagement with treatment. Research shows 56% of patients are willing to plan in advance for an unsuccessful cycle, but little is known about their willingness and preferences to be counselled about the possibility of treatment being unsuccessful. Study design, size, duration Cross-sectional, mixed-methods. Bilingual (Portuguese/English), online survey, disseminated via social media (April-December 2021). Eligibility criteria include being aged 18 or older, waiting to/undergoing an IVF/ICSI cycle, or completing one within the last six months without achieving pregnancy. Out of 651 people accessing the survey, 451 consented to participate. From these, 100 did not complete 50% of survey questions, nine did not report on willingness to be counselled, and 342 completed the survey (75.8%, 338 women). Participants/materials, setting, methods Theoretically informed survey. Quantitative questions covered sociodemographic, fertility history and treatment, willingness (yes, no), preferences (by whom, when, why, how), and perceptions (Theory of Planned Behaviour predictors: attitudes, perceived norms, perceived behavioural control; Health belief Model predictors: perceived susceptibility, severity, benefits, barriers) towards being counselled about the possibility of treatment being unsuccessful. Qualitative questions gathered textual data on past experiences of counselling (by whom, topics addressed). Descriptive, logistic regressions, and thematic analysis were used. Main results and the role of chance Participants were on average 36 years old, most resident in Portugal (59.9%) and the UK (37.7%). The majority (97.1%) were in a relationship for 10 years, and 86.3% were childless. Participants were undergoing treatment for on average two years [SD=2.11, 0-12 years]. Most (71.8%) completed at least one cycle in the past, with 93.5% not having achieved a positive outcome. Almost all (93.3%) would like to be counselled for possible unsuccessful treatment. Reported preferences indicated that 78.3% wanted to be counselled by a counsellor/psychologist/psychiatrist; 73.3% before initiating the first cycle; mostly in case of a bad prognosis (79.4%), emotional distress (73.5%) or difficulties in accepting the possibility treatment being unsuccessful (71.2%); and mainly in an individual (M=6.37, SD=1.17; in 1-7 scale) or couple (M=6.34, SD=1.24; in 1-7 scale) session. Willingness was associated with stronger positive attitudes towards counselling (OR[95% CI]; 3.11[2.02-4.78]), higher perceived benefits of discussing psychosocial resources and strategies to cope with the loss (12.83[1.72-95.67]), and lower concerns about counselling triggering negative emotions (0.15[0.03-0.74]). Around one-third (34.9%) reported having been counselled, with thematic analysis showing patients were mostly counselled by their consultant and the main topic addressed was low prognosis, with emphasis being put on a future positive outcome. Limitations, reasons for caution Self-selected sample, mostly composed of female patients who had not yet achieved their parenthood goals. Small number of unwilling participants reduced statistical power. The main outcome variable was intentions and research shows intentions are only moderately associated with actual behaviour. Wider implications of the findings To meet patients’ preferences, fertility clinics should provide more opportunities for patients to discuss the possibility of their treatment being unsuccessful, both before and during treatment. Such counselling should reassure patients they can cope with any treatment outcome and signpost them to coping resources and support sources. Trial registration number Not applicable

P-165 Which are the determining factors influencing the success rate of egg donation programs with imported vitrified oocytes?

Abstract Study question Which are the determining factors influencing the success rate of egg donation programs with imported vitrified oocytes? Summary answer Number of oocytes available after warming, male BMI and semen characteristics are critical parameters influencing reproductive results of oocyte donation programs with imported vitrified oocytes What is known already The use of vitrified oocytes from foreign banks and the performance of ICSI using fresh sperm from the recipient's partner is a widely used method of heterologous fertilisation. Recent evidence has questioned the overall effectiveness of this approach: vitrification and warming may reduce the number of oocytes available for insemination, resulting in a lower rate of live births per cycle. Recent studies have attempted to define the right clinical strategy to improve the effectiveness of oocyte vitrification cycles, stressing the importance of the number of imported oocytes (8-9 oocytes) and transfer to the blastocyst stage. Study design, size, duration Observational longitudinal cohort study of 431 cycles of oocyte donation conducted between January 2015 and February 2019. A total of 398 couples (mean female age: 43.2 ± 3.5, 28-50 years; mean male age: 44.7 ± 6.1, 28-73 years) underwent an IVF cycle with imported donated vitrified oocytes (mean donor age: 25.2 ± 3.5, 19-34 years). All consecutive oocyte donation cycles conducted at the centre for Reproductive Medicine of the European Hospital in Rome were included. Participants/materials, setting, methods In order to assess which factors are associated with the various outcomes, uni-and multi-variable analyses were conducted. In the multivariable analyses, variables that showed a p value&amp;lt;0.1 in the univariable analyses were included in the final model. The results were presented as Odds Ratio (OR). The corresponding 95% Confidence Interval (95% CI) was also exposed. A p value &amp;lt;0.05 was considered statistically significant. All analyses were performed with STATA v16.1 statistical software. Main results and the role of chance A univariate analysis was carried out showing that among the demographic characteristics studied, the only one that proved significantly able to influence the outcome of the pregnancy test was male BMI. In 49% of unsuccessful cycles, the male BMI was above 25 (p = 0.03). The correlation is confirmed when comparing cycle outcomes in couples with normal/underweight vs overweight/obese men (p = 0.03). The relationship between female or donor BMI and treatment outcome, however, was not statistically significant. The day on which embryo transfer is performed affects the outcome of the cycle: transferring on day 2 compared to day 5 reduces the probability of clinical pregnancy (ET in day 2= positive clinical pregnancy in 4/16 (25%); ET in day 3= 158/307 (51.4%); ET in day 5=40/67 (59.7%). The relationship between male BMI classes and sperm parameters was studied: the distribution of concentration is different in the 3 BMI groups (p = 0.011); in particular, obese men have a significantly lower concentration than normal-weight men (p = 0.006 after Bonferroni correction). There were no statistically significant differences in volume (P = 0.722), morphology (p = 0.100) and motility (p = 0.179), although there was a downward trend in motility, with a reduction in obese subjects compared to normal weight. Limitations, reasons for caution This is an observational study and our findings are in contrast with previous studies which do not show any correlation between male partner BMI categories and reproductive outcomes in egg donation programs. Wider implications of the findings Our study shows that the number of oocytes available after warming, male BMI, semen characteristics and blastocyst transfer are critical parameters able to influence the reproductive outcomes of egg donation programs with imported vitrified oocytes. Trial registration number Not applicable

Which factors influence the success rate of egg donation programmes with imported vitrified oocytes?

Research questionWhich factors influence the success rate of egg donation programmes with imported vitrified oocytes? DesignObservational longitudinal cohort study of 431 oocyte donation cycles conducted between January 2015 and February 2019. A total of 398 couples underwent an IVF cycle with imported donated vitrified eggs. All consecutive oocyte donation cycles conducted at the Centre for Reproductive Medicine of the European Hospital in Rome, Italy, were included. ResultsA univariable analysis was conducted. Among the demographic characteristics studied, body mass index (BMI) was significantly able to influence outcome. In 49% of unsuccessful cycles, men were overweight, compared with 39.4% in cycles with a positive beta-HCG test (P = 0.03). The relationship between female or donor BMI and treatment outcome, however, was not statistically significant. The day on which the embryo is transferred affects the outcome of the cycle: transferring on day 2 versus day 5 reduces the probability of clinical pregnancy. The relationship between male BMI classes and semen parameters was studied: obese men have a significantly lower sperm concentration than normal-weight men (P = 0.006 after Bonferroni correction). No statistically significant differences were found in semen volume (P = 0.722), sperm morphology (P = 0.100) and motility (P = 0.179) in obese men compared with normal weight men. ConclusionIn addition to the number of oocytes available after warming, male BMI, semen characteristics and blastocyst transfer are critical parameters able to influence the reproductive outcomes of egg donation programmes with imported vitrified oocytes.

O-236 The clinical and morphokinetic factors indicating a risk of pregnancy loss after a euploid embryo transfer

Abstract Study question Are there any clinical and morphokinetic factors which may affect the pregnancy outcome after a euploid embryo transfer? Summary answer Body mass index (BMI), endometriosis, the history of recurrent pregnancy losses and the number of previous frozen-thawed unsuccessful embryo transfer (FET) cycles impact pregnancy outcomes. What is known already Preimplantation genetic testing for aneuploidy (PGT-A) is largely used for various indications to detect chromosomal abnormalities in assisted reproductive technologies (ART). The most common reason for the first trimester pregnancy losses is chromosomal abnormalities. However, the factors that cause pregnancy loss after a euploid embryo transfer are not fully understood. Study design, size, duration The pregnancy results of all single euploid embryos tested with next generation sequencing (NGS) in Istanbul Memorial Hospital between January 2017 and March 2020 were evaluated in this single center retrospective cohort study. The cases that resulted in pregnancy below the age of 43 were analyzed according to outcomes; biochemical pregnancy loss (Group 1), clinical pregnancy loss (Group 2) and live birth (Group 3). Participants/materials, setting, methods The transfer of 2041 single euploid embryos resulted in 1492 pregnancies. The clinical and morphokinetic parameters observed using time lapse imaging (TLI) were compared among the three groups. Main results and the role of chance The overall pregnancy rate was 73.1%, the rates of biochemical pregnancy losses and clinical losses were 9.7% and 11.4% respectively. The live birth rate was 58.5%. The indications for PGT-A were as follows; recurrent pregnancy losses (RPL) (14.9%), recurrent implantation failure (RIF) (11.7%), advanced maternal age (AMA) (28.6%), a history of abnormal fetal karyotype or single gene defects (12.1%). In 32.6% cases PGT-A was performed to reduce time to pregnancy. There were no differences in terms of female age, AMH, the diagnosis or the duration of infertility, the mean numbers of oocytes retrieved, mature and fertilized oocytes. However, BMI values, the presence of severe endometriosis, including adenomyosis, the history of recurrent pregnancy losses and the number of previous unsuccessful FET cycles were significantly higher in Groups 1 and 2. When pregnancy losses were evaluated according to PGT indications, patients with a history of RPL had a significantly higher pregnancy loss rate (27.8%) compared to the other groups: AMA (19.6%), RIF (19.4%), genetic factors (21.6%) and cases where PGT was performed to reduce time to pregnancy (16.4%) (p &amp;lt; 0.05). When morphokinetic parameters were evaluated, they were found to be not significantly different in the three groups (p &amp;gt; 0.05). Limitations, reasons for caution The retrospective nature of the data is the major limitation of the study. On the other hand, the strength of the study is the large number of PGT-A tested embryos from a single center which used the same laboratory conditions. Wider implications of the findings PGT-A is widely used to avoid pregnancy losses. However, BMI values, the presence of severe endometriosis, including adenomyosis, the history of recurrent pregnancy losses and the number of previous unsuccessful FET cycles should be taken into consideration during counselling and/or treatment. Trial registration number not applicable

Patient willingness, preferences and decision-making about planning for three complete cycles of IVF/ICSI treatment.

Patient willingness, preferences and decision-making about planning for three complete cycles of IVF/ICSI treatment.

Микробиом эндометрия у женщин с многократными неудачами экстракорпорального оплодотворения

Objective. To assess endometrial microbiome in women with infertility and multiple failed in vitro fertilization (IVF) cycles. Patients and methods. The study included 42 women; group 1 consisted of 22 women aged 20 to 42 with infertility and repeated unsuccessful IVF cycles; in group 2 (control), there were 20 healthy women aged 20 to 42 years, planning pregnancy. Microbiome samples for the study were taken from 20 to 24 days of the menstrual cycle. Results. Higher relative concentrations of Lactobacillus iners, Lactobacillus acidophilus, Lactobacillus jensenii, Lactobacillus crispatus, Prevotella melaninogenica, Bacteroides vulgatus, Corynebacterium bouchesdurhonense, Bacteroides caccae, Bifidobacterium gallinarum, Bifidobacterium adolescentis were revealed in the group of healthy women without aggravating factors in obstetric and gynecological medical history. Higher relative concentrations of Methylobacterium aerolatum and Comamonas testosteroni were found in women in group 1. A distinctive feature of endometrial microbiota in women in this group was the presence of Streptococcus spp. and Gardnerella vaginalis in low concentrations. The average relative representation of the genus Lactobacillus was 34.4% in group 1 and 63.0% in group 2. In general, the composition of the uterine microbiome contained bacteria characteristic of oral and intestinal biotopes. Conclusion. Women with multiple failed IVF cycles have greater biodiversity than healthy women. The presence of high concentrations of Lactobacillus may be a marker of favorable reproductive outcomes. Key words: endometrial microbiome, failure, in vitro fertilization, Lactobacillus

Интраовариальная аутоплазмотерапия у пациенток с низким овариальным резервом

Objective. To evaluate the efficacy of Intraovarian autoplasmotherapy (platelet-rich plasma/PRP) in the activation of ovarian function in patients with diminished ovarian reserve and “poor” response in the in vitro fertilization (IVF) cycles, as well as its influence on the quality of life. Patients and methods. A total of 120 patients with diminished ovarian reserve and a history of IVF cycle failure who refused to use donor oocytes were included in the study. All patients underwent intraovarian PRP therapy based on the proprietary technology. The quality of life, the ovarian function, and the results of the embryo stage in the IVF cycle were monitored for 6 months. Results. The conducted study demonstrates a positive effect of intraovarian PRP therapy on the functional state of the ovaries and on the results of the embryo stage in IVF in the cohort of patients with diminished ovarian reserve and “poor” response in previous unsuccessful IVF cycles. The findings also indicate changes in the quality of life, an improvement in sexual function, and positive dynamics in the emotional state. Conclusion. Intraovarian PRP therapy allows patients with infertility and diminished ovarian reserve to avoid using donor oocytes and to obtain their own genetic material. This technology has a positive effect on the quality of life, having a certain anti-age effect in all groups of examined women, the duration of which has yet to be clarified. Key words: infertility, “poor” response, intraovarian PRP therapy, IVF cycle failure, diminished ovarian reserve

Dropout of infertility treatments and related factors among infertile couples

BackgroundDropout of infertility treatments is a global issue and many factors play role in this phenomenon. It is one of the most challenges in life of infertile couples. The purpose of this study was to determine dropout rate and related factors/reasons in the world and in Iran.MethodsWe will conduct a mixed method study with sequential exploratory design (systematic review, qualitative and quantitative phase). In the first stage a systematic review on dropout rate of infertility treatments and related factors will be done. In second stage (quantitative–qualitative study), a retrospective cohort study will be conducted on infertile couples to determine dropout rate of infertility treatments. The follow-up period to assess the discontinuation of treatment in patients, who have discontinued the treatment, will be considered 6 months after the treatment cessation. Data would be analyzed by descriptive statistics. We want to determine proportion and percentage of discontinuation rate among different groups with different causes of infertility. Then, we also will use Chi-square test to compare discontinuation rates among these groups. In qualitative section of second stage, semi-structured interviews would be performed with infertile female who had the history of infertility treatments failure. In this stage, participants will be selected using purposeful sampling method with maximum variation in terms of age, education, occupation, type of infertility, type of treatments, number of unsuccessful treatment and infertility duration. Data would be analyzed using conventional content analysis.DiscussionDetermining dropout rate and its related factors/reasons would be helpful for future studies to plan suitable interventions for supporting infertile couples. It also helps politicians to have a better understanding of infertility and its consequences on infertile couple’s life.Plain English SummaryIn today’s world, infertility is a common phenomenon due to postponement of childbearing following the older age of marriage, tendency to reach higher educational level, economical problems and etc. Infertility brings many challenges and stresses to the individuals by itself and it is very hard to cope with. The problem gets worse, when it is associated with failure in treatments. Many of infertile couples cannot tolerate this failure and may decide to discontinue treatments before achieving pregnancy for ending many stressors which are associated with treatments. As we know, childbearing and having at least one child has important position in some societies such as Iranian culture; so ending the treatment before achieving optimal result may have some adverse consequences in the families such as divorce, remarriage, family conflicts, et. Absolutely many factors play role in dropout of infertility treatments, and many studies around the world have suggested many factors/reasons in dropout of infertility treatments, but there are still many gaps about this subject, especially among Iranian society. This study would be conducted in three consecutive stages, in the first stage; we will do a complete review of existing studies of the world to find out related factors/reasons of dropout in detail. In second stage, dropout rate of infertile couples (380 couples) after at least one unsuccessful cycle of treatment would be achieved by assessing medical records and telephone interview. Data of the first and second stage will help us to have better vision about the issue of dropout and would be used to construct a semi structured interview for the last stage. And finally in the third stage, reasons of dropout would be asked by an in depth interview from infertile couples. We hope the information from this study will help politicians better understand and plan for dropout of treatment.