Reproductive Technology Treatment Research Articles

P-727 The impact of antidepressants and anxiolytics on assisted reproductive technology treatment outcomes

Abstract Study question Does antidepressant and anxiolytic use impact the chance of live birth after assisted reproductive technology (ART) treatment? Summary answer For women using antidepressants, ART treatment is as successful as for others. However, concomitant anxiolytic use was associated with failure to succeed. What is known already Infertility and depression are prevalent disorders in women of reproductive age and may occur coincidently. Antidepressants constitute the mainstay in treatment for moderate-severe depression, and selective serotonin reuptake inhibitors (SSRIs) are among the most commonly used antidepressants because they, in general, cause few side effects. However, antidepressant use in women undergoing ART treatment may be considered to balance the possible risks of untreated depression against fetal drug exposure and the efficacy of ART treatment. Furthermore, up to 50% of patients with depression also meet the criteria for anxiety disorders and may be treated with anxiolytics. Study design, size, duration This is an observational cohort study based on the Danish health registries. The use of antidepressants, i.e. as current or recent users, and anxiolytics or hypnotics at embryo transfer was obtained from the prescription register and information on all ART treatments and childbirths between 2006 and 2019 from the Danish ART register and the Danish birth register. Participants/materials, setting, methods The study population included 130,170 embryo transfers in 48,156 women undergoing ART treatment. A total of 1505 women were exposed to antidepressants at the time of embryo transfer, and 1160 women were recent users who discontinued before embryo transfer. We used mixed-effects logistic regression analyses. The association between antidepressants and anxiolytics respectively and ART was analyzed taking potential confounders into account estimating the odds ratios(OR) of either a biochemical pregnancy, clinical pregnancy, or live birth. Main results and the role of chance The adjusted OR(aOR) and corresponding 95% confidence interval (CI) of a biochemical-, and clinical pregnancy in women with current use of antidepressants at time of embryo transfer were 0.87 (95% CI: 0.73-1.04) and 0.84 (95% CI: 0.57-1.20), respectively, and 0.90 (95% CI: 0.67-1.19) for live birth. For women who discontinued antidepressant use before embryo transfer (labeled recent users), the aORs for a biochemical-, clinical pregnancy and live birth were 0.95 (95% CI: 0.76-1.17), 0.71 (95% CI: 0.46-1.09) and 1.02 (95% CI: 0.72-1.45), respectively. When analyzing women who use or recently used antidepressants in combination with anxiolytics or hypnotics the chance of a live birth was decreased markedly with an aOR of 0.15 (95% CI: 0.04-0.51). Based on nationwide data from more than a decade of ART treatments, we found that the use of antidepressants at the time of embryo transfer was not associated with a decreased chance of biochemical or clinical pregnancy, or live birth. However, when women treated with antidepressants also used anxiolytics or hypnotics, the chance of a live birth was significantly decreased though based on a limited number of patients suggesting a point of further investigation and attention. Limitations, reasons for caution As in all observational studies, it can never be ensured that the patients take the medicine, but we used information on prescriptions for antidepressants/anxiolytics from the prescription register using at least two redeemed prescriptions within 182 days before, and until 182 days after the date of embryo transfer. Wider implications of the findings Use of antidepressants at the time of embryo transfer was not associated with a decreased chance of biochemical or clinical pregnancy, or live birth. However, when antidepressants are used concomitantly with anxiolytics or hypnotics, the chance of live birth is significantly decreased suggesting the need for further investigation and attention. Trial registration number The study was funded by The Region of Southern Denmark and Merck.

O-032 Intravenous immunoglobulin and prednisolone to women with unexplained recurrent pregnancy loss undergoing assisted reproductive technology treatment: a randomized, double-blinded, placebo-controlled trial

Abstract Study question Does intravenous immunoglobulin (IVIG) and prednisolone in combination affect ongoing pregnancy rate among patients with recurrent pregnancy loss (RPL) after assisted reproductive technology (ART) treatment? Summary answer The results of this trial will provide important information about whether immunomodulatory treatment to RPL patients undergoing ART treatment can increase clinical pregnancy rate. What is known already Two retrospective cohort studies suggest that IVIG and prednisolone in combination result in a 34-37% live birth rate in RPL patients undergoing ART which is higher than the expected 12% for patients with RPL after ART. A randomized controlled trial (RCT) testing IVIG in RPL patients conceiving naturally indicated that very early administration of IVIG caused more positive effects than late administration, and prospective cohort studies suggest that treatment efficacy depends on presence of immune disturbances. No RCT has tested the IVIG/prednisolone combination starting before implantation and continued in very early pregnancy for RPL patients undergoing ART. Study design, size, duration In a randomized, double-blinded, placebo-controlled trial, patients undergoing IVF/ICSI/FET were treated with 400mg/kg IVIG and 5-10mg/day oral prednisolone or IV human albumin and oral placebo between January 2021 and March 2024. Oral treatment was administered from day one of menstrual cycle to GW 8 + 4, while IV treatment was given once in a short time interval before or after embryo transfer and repeated three times before GW 8 + 0. Primary outcome was ongoing pregnancy in GW 12 Participants/materials, setting, methods Seventy-four women <41 years old with ≥2 consecutive biochemical or clinical early pregnancy losses after ART were randomized 1:1 and underwent trial treatment along with their next IVF/ICSI/FET treatment. Patients were followed with weekly ultrasound scans in first trimester, however, if no implantation occurred, trial participation ended, and no re-entry was allowed. Exclusion criteria included antiphospholipid syndrome, BMI >35, uterine malformations, parental chromosomal translocations, AMH <4 pmol/l, drug contraindications, thyroid disease, and prior IVIG treatment. Main results and the role of chance Seventy-four patients have been randomized, and currently we are awaiting the last two patients to complete the treatment protocol before the code can be disclosed. Blinded interim analysis after inclusion of 38 patients showed no serious adverse events and an ongoing pregnancy rate of 30.0% and 9.5% (RR 1.8, 95% CI 1.0-3.1, Fisher’s exact test: p = 0.13), in the two allocation groups, respectively. Final, unblinded data on ongoing pregnancy rate, miscarriage rate and adverse events will be presented at the Congress if selected for presentation. Limitations, reasons for caution No published study has tested the same treatments in comparable patient groups which could have been the basis for the sample-size calculation, and the study is therefore at risk for being underpowered to evaluate the treatment effect in patients suffering from a combination of infertility, recurrent implantation failure, and RPL. Wider implications of the findings Blood samples were collected before first IV treatment and approximately 4 weeks later, which allow analysis for immunological disturbances and searching for biomarkers identifying those who will benefit from the treatment. This treatment could potentially increase success rate in patients undergoing ART after multiple unsuccessful treatment attempts. Trial registration number NCT04701034

O-105 Contribution of ART to fertility rates and family size

Abstract In the last three decades declining fertility has become an increasing global trend. One-half of the global population today lives in countries where the period Total Fertility Rate is below 2.1 births per woman. Many countries in Europe and Asia are experiencing “ultra-low” fertility rates of 1.0-1.4 births per woman. This decline in births creates both social and economic challenges. In addition, most countries have gone through a long period of increasing average age at birth. The shift in births at older ages has been accompanied by a concomitant decline in completed family size. As the average age at having children has increased over time, the proportion of women experiencing difficulty in achieving a pregnancy has also increased, with assisted reproductive technology (ART) treatments becoming increasingly important in counteracting this decline. However, the demographic impact of ART widely varies across countries, with the proportion of babies born as a result of ART, ranging from almost 10% of birth in in some European countries to < 1% in Latin America and 2% in the USA. ART is increasingly being raised as a potential policy tool to increase fertility. While ART can broaden the range of possible responses to low fertility rates, there are a number of challenges in quantifying contribution to fertility rates. There are also a number of important unintended consequences that need to be taken into account when trying to estimate their effectiveness as a policy tool to increase fertility. In this presentation, the evidence for the contribution of ART to total and age-specific fertility rates in different settings will be summarized and compared with other pronatalist policies. The contribution of ART and other forms of fertility treatment to completed family size and childbearing timing will also be described and discussed. Assisted reproduction is making a modest and increasing contribution to the fertility rate of high-income countries, but its potential impact should not be overestimated.

O-097 Implantation-on-chip: precise quantification for functional implantation failure studies

Abstract Study question How can we obtain precise quantitative information about what factors causally affect the first steps of embryo implantation and Repeated Implantation Failure (RIF)? Summary answer We have developed a personalized implantation-on-chip model, based on novel in vitro models of the endometrium and the embryo (i.e., blastoids), to quantify functional attachment. What is known already RIF is a multifactorial condition characterized by the persistent inability to achieve clinical pregnancy, despite the transfer of high-quality embryos. Typically diagnosed within the context of assisted reproductive technology (ART) treatment, RIF arises due to disruptions in the endometrium receptivity, the interaction between the endometrium and early embryo, or both. The endometrial factors of RIF can be linked to disrupted hormone signaling and timing, impacting endometrial receptivity and therefore the chance of conceiving. Synchronization between the blastocyst and receptive endometrium is critical for successful implantation. Ethical and technical limitations of in vivo patient research restricts our understanding of implantation failure. Study design, size, duration Organoids were transformed into endometrial monolayers within custom-made microfluidic chips. These monolayers on chip were either treated with EPCX; β-estradiol (E2), progesterone (P4), 8-Br-cAMP (C) and XAV939 (X) (referred as induced), or not treated (referred as control) for 6 days. Large number of blastoids (>100) were then infused per chip followed by 48 hours of culture. Then, the rate of adhered blastoids was measured under exposure to controlled flow rates (50, 100 and 400 µl/min). Participants/materials, setting, methods Human naïve induced pluripotent stem cells were used to form blastoids, stem cell-based models of the blastocyst, to alleviate the ethical concerns and limited access of blastocysts. Blastoids present the three blastocyst lineages required for development and offer limitless production in number. Endometrium organoids, derived from parous fertile patients (N = 3), was used to recapitulate molecular and functional receptivity by RT-qPCR-based gene expression measurements and microfluidic flow-dependent adhesion rates of blastoids, respectively. Main results and the role of chance 2-D monolayers that maintained their epithelial identity and responsiveness to hormones as measured by expression of receptivity-related genes (PAEP, SPP1 and GPX3), which were upregulated in EPCX condition. Further characterization of the epithelial monolayers showed reduced MUC1 expression in the EPCX condition, suggesting increased receptivity. Additionally, reduced acetylated α-tubulin, indicating a reduction in the number of ciliated cells, aligning with our observations. Through controlled exposure to increasing flow, functional receptivity through blastoid adhesion was precisely quantified, which showed 35% of the blastoid remained adhered in the EPCX condition, whereas only 15% remained adhered in the control. A 48 hours culture period presented a blastoid-induced endometrial gap in 45.54% of the remaining blastoids, with an average of 110.287,3 µm2 in surface area, which was associated with trophoblast cells infiltration, measuring an average migration distance of 174.8 µm from the pluripotent cell core. In addition, the substantial difference in receptivity profiles established a baseline for subsequent experiments, including the study of temporal alterations in hormone signaling, a potential problem associated with RIF. Hormone administration variations, timing and a progesterone-deficient condition are currently being tested. These results will underscore the sensitivity of our system and demonstrate its potential for applications in drug screening. Limitations, reasons for caution Currently our endometrium model consists of epithelial cells, which are only representative for implantation to a limited extent. A more complex endometrium including stromal, endothelial and immune cells could highly increase the physiological relevance of the model. Wider implications of the findings This platform has the potential to provide a diagnostic platform to identify patients with endometrium epithelium-associated RIF and factors that may improve embryo receptivity and implantation. Moreover, this approach has the potential to be pivotal for toxicological studies, and furthering our understanding of human reproductive biology. Trial registration number not applicable

O-018 Utilisation of second successive ejaculate as a way to overcome poor semen parameters for couples who wish to undergo conventional-IVF

Abstract Study question Can a second successive-ejaculate (SSE) be an option for patients with poor sperm parameters (PSPs) on ovum pick-up (OPU)-day who prefer to undergo conventional-IVF (c-IVF)? Summary answer SSE can be a valid option for patients with PSPs who do not wish to undergo ICSI as an assisted reproductive technology (ART) treatment. What is known already ART is applied when first-line treatment for infertility (timed intercourse or intrauterine insemination) is unsuccessful. The male partner is requested to follow ejaculatory abstinence, which according to the WHO guidelines is 2-7 days, while ESHRE recommends 3-4 days. Among these couples there are cases that require ICSI due to semen analysis with PSPs on the day of OPU. However, some couples are reluctant to undergo ICSI and prefer c-IVF as a treatment method. For those cases, we request a second semen sample on the same day (time interval: 1-4 h) and c-IVF is performed using the two ejaculates combined. Study design, size, duration This is a single-centre retrospective study employing 212 semen from male partners with PSPs in the first semen collection on the OPU-day and subsequently, an SSE was requested in order to perform c-IVF according to patients’ wishes. The data were collected from May 2006 to October 2023 in our clinic (SSE-group). The Control group included 271 semen samples from men where c-IVF was conducted using one ejaculate from January to December 2021 in our clinic. Participants/materials, setting, methods The sperm parameters were analysed according to the WHO manual for the examination and processing of human semen and compared between the first and second ejaculates in the SSE-group. Fertilisation rate (FR), percentage of clinically utilised embryos and clinical pregnancy rate were compared between the SSE-group and the Control group. The SSE-group had 254 ART-cycles and the mean maternal age was 36.8±4.9y.o. The Control group included 432 ART-cycles and the mean maternal age was 38.1±5.2y.o. Main results and the role of chance In SSE-group the semen volume of the first ejaculate was significantly higher compared to the second ejaculate (P< 0.0001). The sperm concentration and sperm motility were significantly higher in the second ejaculate compared to the first one (P<0.0001). In the same fashion, the total-motile sperm-count was significantly higher in the second ejaculate compared to the first (P=0.01). All the semen parameters in the Control group were significantly higher compared to both first and second ejaculates from the SSE-group (P<0.00001). The normal FR was significantly higher in the Control group compared to the SSE–group (P<0.01). On the other hand, there was no significant difference in the percentage of embryos that could be utilized (cryopreserved + freshly-transferred) between the two groups (P=0.218). Pregnancy rate for fresh embryo transfers (ETs) was significantly higher in the SSE-group compared to the Control (P=0.005), while there was no significant difference between the two groups for pregnancy rate for frozen/thawed ETs (P=0.728). The main strength of our study is that the utilisation of the SSE combined with the first ejaculate did not decrease the pregnancy rate for the couples with PSPs that wished to follow c-IVF as their treatment and it could actually provide an effective option for them. Limitations, reasons for caution SSE may improve the sperm parameters and give the opportunity to infertile couples to undergo c-IVF according to their wish. However, since the FR was lower in the SSE-group, it is of paramount importance to provide sufficient explanation to those couples and obtain their consent when requesting an SSE. Wider implications of the findings Overall, SSE had positive effect to a large number of parameters evaluated in this study. Additionally, the rate of utilised embryos was similar between the two groups. Two successive-ejaculates combined can be employed without any negative impact for couples with PSPs on the OPU-day that are reluctant to undergo ICSI. Trial registration number not applicable

O-067 An update from the international reproductive health education collaboration

Abstract Most people want children, but many do not achieve their parenthood goals. Research shows that both men and women have limited knowledge about fertility and the factors that affect it. This includes poor knowledge about the impact of age, the most important determinant of the chance to conceive and have a healthy baby. As age at first birth is increasing in many countries, people increasingly seek assisted reproductive technology (ART) treatment due to age-related infertility. To allow people to make informed decisions about if and when to have children and to avoid age-related infertility, they need evidence-based and accessible information about fertility. Fertility awareness is defined by the World Health Organisation as ‘the understanding of reproduction, fecundity, fecundability, and related individual risk factors (e.g. advanced age, sexual health factors such as sexually transmitted infections (STIs), and lifestyle factors such as smoking, obesity) and non-individual risk factors (e.g. environmental and workplace factors); including the awareness of societal and cultural factors affecting options to meet reproductive family planning, as well as family building needs’. In 2019, an international collective of reproductive health researchers and health professionals convened to promote fertility education for the public, teachers, and health professionals. Initially called the International Fertility Education Initiative (IFEI), in 2022 the group integrated into ESHRE. In 2023, the group rebranded as the International Reproductive Health Education Collaboration (IRHEC) (www.eshre.eu/IRHEC) to reflect a life course perspective that goes beyond childbearing and includes education about all aspects of reproductive health, from puberty to menopause. The mission statement of the IRHEC is ‘To increase reproductive health awareness using the life course approach, in order to improve reproductive health and facilitate decision-making in family planning among adolescents, people of reproductive age, primary healthcare, education professionals, and policymakers through development, evaluation and dissemination of inclusive educational resources.’ We aim for our website to be a repository for a range of reproductive health educational resources for the public, health and education professionals, and researchers. This includes some resources developed by the group. In this first IRHEC report to the ESHRE conference we will describe the committee structure, the processes for joining the IRHEC Network and for nominations and elections of committee members and introduce current IRHEC committee members. We will also provide updates on completed resources to be launched during 2024 and on current and potential future projects including: • An updated fertility education poster for young people. It is based on a poster developed in 2019 which has been redesigned in response to research conducted with young people in Denmark, Sweden, and the UK. The poster is available in many different languages on the IRHEC website. • Twelve information leaflets with more in depth information on various aspects of reproductive health which have been co-designed with young people. These are also available and free to download from our website. • After years of working with schools, and a public consultation last year, IRHEC has developed a resource to help teachers deliver reproductive health education to students. It is freely available to all teachers around the world and can be used in full or in part depending on teachers’ needs. • Preparations are underway to seek funding to evaluate the teachers’ resource. We plan to use qualitative research in the first instance to explore teachers’ views on the usefulness of the resource, what parts they would use, and whether the topics covered, and the level of detail are appropriate. • We are also examining how social media can be used to deliver reproductive health education. Through this work we want to empower everyone with evidence-based education on reproductive health.

O-188 Conventional in vitro fertilisation versus intracytoplasmic sperm injection in first cycle patients without severe male factor infertility (INVICSI): a randomised, controlled, open-label, multicentre trial

Abstract Study question Is the cumulative live birth rate (CLBR) after ICSI superior to conventional IVF (c-IVF) in first cycle fertility patients without severe male factor infertility? Summary answer In couples without severe male factor infertility, ICSI does not improve the CLBR compared to c-IVF after transfer of embryos from the first oocyte collection What is known already The ICSI procedure, originally developed for addressing severe male factor infertility, has seen expanded utilisation across various causes of infertility. Large retrospective studies and a recent randomised controlled trial (RCT) demonstrated comparable reproductive outcomes between ICSI and c-IVF in couples without male factor infertility. In approximately half of infertility cases, a male factor is involved, with about one-third attributed to male factor alone. Despite this, ICSI currently constitutes two-thirds of all assisted reproductive technology treatments worldwide Study design, size, duration Open-label, two-armed, multicentre RCT. A sample size of 784 women was required to detect a clinically relevant change of 10 percentage points with 80% power. Accounting for an expected 5% exclusion rate (dropouts and unexpected severely decreased quality sperm samples on the day of oocyte retrieval), 824 women were recruited from six public fertility clinics in Denmark between Nov 29, 2019, and Dec 14, 2022 Participants/materials, setting, methods Eligible participants were women aged 18-42 years and in their first treatment cycle with a partner/donor with normal or lightly to moderately decreased sperm quality. Randomisation was performed in a 1:1ratio between ICSI and c-IVF. The primary outcome was CLBR. Follow-up continued until the primary outcome was achieved or for a minimum of one year after the last participant’s inclusion.The primary outcome was assessed in an intention to treat (ITT) and a per protocol analysis Main results and the role of chance In total, 414 and 410 women were randomised to ICSI and c-IVF, respectively. Results include fresh as well as frozen-thawed embryo transfers from the first oocyte collection and are displayed as ITT. All transfers were elective single embryo transfers or single embryo transfers. The cumulative probability of achieving a live birth for couples/women undergoing ICSI was not different compared to those undergoing c-IVF (CLBR: ICSI 42.0% vs. c-IVF 46.6%, Risk ratio: 0.90, 95% CI: 0.77-1.05). The median time from inclusion to live birth did not differ between ICSI and c-IVF (309 days (IQR 268-378) vs 308 days (IQR 269-356); p = 0.12). Total fertilisation failure was seen in 4.9% of the ICSI group compared to 3.8% in the c-IVF group (Risk ratio: 1.29, 95% CI: 0.68-2.54) Limitations, reasons for caution This study was designed with 80% power to identify a 10% percentage point difference in CLBR between ICSI and c-IVF. We cannot dismiss the possibility of a smaller difference between the two methods Wider implications of the findings Our study, supported by prior research, shows that c-IVF rather than ICSI should be the first choice in initial cycles for patients without severe male factor infertility. Fertility staff should inform first cycle patients that ICSI does not increase the live birth rate for couples without severely decreased sperm quality Trial registration number NCT04128904

P-454 The effects of PLISSIT model based sexual counseling on sexual function and satisfaction in infertile couples

Abstract Study question Does a sexual counseling program based on the PLISSIT model improve the sexual function and satisfaction in infertile men and women? Summary answer PLISSIT model based sexual counseling for infertile couples with sexual dysfunction and low sexual satisfaction, positively affected the sexual function and satisfaction of the couples. What is known already Studies indicate that infertile couples experience more sexual problems than fertile couples due to the physical, psychological, and marital challenges of assisted reproductive technology treatments. Several sexual counseling models are recommended for discussing sexual problems with patients. PLISSIT model (Permission, Limited Information, Specific Suggestions, and Intensive Therapy) have been demonstrated to be effective in improving sexual function. However the effects of PLISSIT model has not been evaluated in infertile couples with sexual problems. Study design, size, duration This randomized-controlled study was conducted between August 2019 - February 2020 in a fertility clinic of a university hospital in Istanbul. With a pre-study screening, 60 infertile couples with sexual dysfunction (women with a total score of ≤ 26.55 on the Female Sexual Function Index-FSFI and men with a score of ≥ 11 on the Arizona Sexual Experiences Scale-ASEX were included in the study. Participants were randomized for the counselling (30 couples) and control (30 couples) groups. Participants/materials, setting, methods Couples in counselling group were interviewed in 6 sessions (first assessment, 3 counseling sessions one week apart, 1 phone call in the second month and last assessment in the third month), and couples in control group were interviewed in 3 sessions (first assessment - 1 phone call in the second month and last assessment in the third month). FSFI, ASEX, Beck Depression Inventory-BDI, New Sexual Satisfaction Inventory-NSSI, Fertility Problem Stress Scale-FPSS were used for evaluation. Main results and the role of chance BDI total mean scores of women and men in the first asessments were similar in the counselling and control groups. In the final evaluations of the groups, women who received sexual counseling had better total scale scores and sub-dimension scores of FSFI and NSSI than the control group, and the ISS total scale scores and sub-dimension scores of women were lower than the control group. In the final evaluations of men in counselling group, mean ASEX score was positively lower, the total scale and sub-dimension scores of the NSSI were higher and the ISS total scale and sub-dimension scores were lower than the control group. Limitations, reasons for caution The long-term results of sexual counseling were not followed and the long term intensive therapy phase could not be carried out in this study. Results are limited to primary infertile couples with sexual problems in the setting of this reserch. Wider implications of the findings In order to comprehensively evaluate couples while providing sexual education and counseling with a planned and systematic approach, using counselling models for sexual function such as the PLISSIT model is recommended. Trial registration number ClinicalTrials Protocol ID: 13022260-300-108795

Differential expression of CYP19A1 and lncRNA-CTBP1-AS in the granulosa cells of women with polycystic ovary syndrome

Background: Hyperandrogenism is the basic indicator of polycystic ovarian syndrome (PCOS) and a key factor in its pathological processes. Patients with PCOS have higher testosterone levels along with a decline in the estradiol/testosterone ratio, which may indicate an aromatase dysfunction. The aim of the study: Investigating the expression levels of CYP19A1 and lncRNA-CTBP1-AS in the granulosa cells (GCs) of women with and without PCOS. Materials and methods: We compared the expression levels of CYP19A1 and lncRNA-CTBP1-AS in granulosa cells from 16 PCOS patients and 20 controls who underwent assisted reproductive technology (ART) treatment at the Center for Human Reproduction and IVF (Rostov-on-Don, Russia) using quantitative real-time PCR. Results: We observed a significant downregulation of CYP19A1 expression in the GCs of PCOS patients, with expression levels approximately 4.7 times lower compared to the control group. Furthermore, we found a positive correlation between CYP19A1 expression and the E2/T ratio in PCOS patients. Conversely, PCOS patients exhibited a remarkable upregulation of CTBP1-AS expression in their GCs, with levels up to 23 times higher than those in the control group. Importantly, we also identified a significant negative correlation between the expression level of CTBP1-AS and CYP19A1 in the GCs of PCOS patients. Conclusion: Our results indicate a potential regulatory role of CTBP1-AS in CYP19A1 expression and suggest its involvement in the pathogenesis of PCOS.

Body Mass Index as a Factor Influencing Oocyte Competence and Implantation Potential – Distribution and Results in 4,882 Women Undergoing Fertility Treatment

Abstract Introduction The large amount of excess adipose tissue affects negatively every single step of the assisted reproductive treatment process – from the controlled ovarian hyperstimulation (COH) to obstetric complications and health consequences for the fetus. A number of scientific data show correlation between impaired clinical pregnancy rates (CPR) and obese patients maintaining high body mass index (BMI). The debate whether high proportion of body fat negatively affects oocyte quality or only impacts endometrial receptivity remains open. Aim The aim of this study is to investigate the specific effect of the different BMI range in patients undergoing assisted reproductive technology (ART) treatment with reference to oocyte quality, fertilization capacity and Implantation potential. Materials and methods We analyzed a total of 4,882 women from partner couples who underwent ART treatment. Height and weight data were entered at the start of the in vitro fertilization (IVF) procedure. According to their BMI the female patients were divided in four distinct groups: in group 1 (underweight and BMI below 18.5 kg/m2) – 498 women, group 2 (normal range from 18.5 to 24.9 kg/m2) – 3021 women, group 3 (overweight with BMI between 25 – 29.9 kg/m2) – 789 women and group 4 (obese with BMI over 30 kg/m2) - 484 women. Results Distribution of the women in different BMI groups indicates that most of the Bulgarian patients undergoing fertility treatment are in the normal range. No association between BMI and ovarian response was found. A total of 33,205 oocytes were obtained after the COH. The mean numbers of the retrieved oocytes were similar (6,85 in group 1; 6,83 in group 2, 6,77 in group 3 and 6,67 in group 4) per woman and the fertilization rate was comparable in the four groups as it varies between 74-75%. Proportional categories of good, fair and bad embryos at cleavage stage were found. On the contrary according to CPR, Statistical difference between normal weight group (34,38%) versus overweight (29,6%) and obese groups (28,80%) (p < 0,05) was found. Conclusion No correlation was found between the number of the retrieved oocytes and BMI values. Statistically lower pregnancy rates were reported in overweight women with BMI ≥ 25 kg/m2 group and further onwards in the obesity group (BMI ≥ 30 kg/m2), which may be associated with impaired endometrial receptivity as a result of abnormally high levels of adipose tissue.

Notice of Retraction: Analysis of Assisted Reproductive Technology Treatment of 126 Uterine Adenomyosis Patients Diagnosed via Ultrasonography

Notice of Retraction: Analysis of Assisted Reproductive Technology Treatment of 126 Uterine Adenomyosis Patients Diagnosed via Ultrasonography

Notice of Retraction: Analysis of Assisted Reproductive Technology Treatment of 126 Uterine Adenomyosis Patients Diagnosed via Ultrasonography

Notice of Retraction: Analysis of Assisted Reproductive Technology Treatment of 126 Uterine Adenomyosis Patients Diagnosed via Ultrasonography

Impact of maternal age on oxidation-reduction potential in follicular fluid and assisted reproductive technology treatment outcomes

Background: Maternal age influenced the quantity and quality of oocytes. The composition of follicular fluid was changed in advanced maternal age. This study was conducted to evaluate changes in redox potential and blastocyst formation potential in older women. Methods and materials: Retrospective study collected data from December 2020 to October 2023 on patients treated with in vitro fertilization with follicular fluid surveyed at the Center for Reproductive Endocrinology and Infertility (HUECREI), Hue University of Medicine and Pharmacy, Hue. Results: Two cohorts comprised the 456 patients: Group 1, consisting of individuals younger than 35 years of age, and Group 2, comprising those 35 years or older. Anti-Müllerian hormone (AMH), initial follicle-stimulating hormone (FSH), and total FSH dose utilized differed significantly between Groups 1 and 2, with median values of 3.79 versus 2.10 ng/mL (P value < 0.001), 225.00 versus 277.50 IU/L (P value < 0.001), and 2025.00 versus 2325.00 IU/L (P value < 0.001), respectively. However, there were no significant differences in ORP, maturation rate, fertilization rate, or blastocyst formation rate between the two age groups. Variations in ORP were only observed among subgroups of patients with the ability to achieve an expected fertilization rate of ≥ 70% in Group 1. Specifically, the subgroup meeting expectations had a lower ORP of 83.00 ± 83.00 mV, in contrast to the non-expectation group which had an ORP of 96.14 ± 83.00 mV, accompanied by a P value of 0.005. The difference of ORP was not observed in the group that reached and did not reach the benchmark embryo formation ≥ 60% in the two age groups. Conclusion: Advanced maternal age have declined in ovarian function but no statistically significant difference in redox potential in follicular fluid has been observed. The fertilization rate and blastocyst formation rate were equivalent across the two age groups of women. The redox potential of follicular fluid was not statistically significant difference between cycles that reached and did not reach the benchmark of blastocyst formation ≥ 60% in the two age groups of women. Key words: Blastocyst, advanced maternal age, oxidative-reduction potential (ORP), in vitro fertilization.

Effect of Platelet-Rich Plasma (PRP) in Combination with Endometrial Scratching for Patients Undergoing Assisted Reproductive Technology Treatment

ABSTRACT Endometrium scratching is a process of intentionally injuring the endometrium, and after scratching the endometrium, platelet-rich plasma (PRP) is inserted into the endometrial wall to improve pregnancy outcome. This case report revolves around a 33-year-old woman and her 38-year-old husband, who have been married for 3 years and were seeking treatment for their secondary infertility. The female had a history of hypothyroidism, and after the investigation, she was diagnosed with hyperprolactinemia. She also had a history of failure in vitro fertilization (IVF) cycles and two recurrent miscarriages upon investigation. The husband was found to have asthanozoospermia. After diagnosis of the female, we started treatment of cabergoline for hyperprolactinemia, a history of unsuccessful IVF cycles, and two recurrent miscarriages upon investigation. After the treatment of hyperprolactinemia in our clinic, we scheduled ovum pick-up and started the stimulation and performed intra-cytoplasmic sperm injection. After 1 month, we scheduled embryo transfer. On day 1, the progesterone scratched the endometrium wall and loaded the PRP to enhance the endometrial wall, and after an interval of 14 days, we checked the β-hCG level in the blood, and the result was positive, that is, the level was 1020 mIU/mL. The successful result of endometrial scratching with PRP improves pregnancy outcomes.

The reproductive journeys of French women over 40 seeking assisted reproductive technology treatments in Spain

Fertility decline is a complex phenomenon resulting from converging social and cultural changes that are governed through politics. As it has been discussed in many studies, the European's low fertility rate goes hand in hand with the trend of maternity postponement. Although in many European countries over the last decades reproduction is envisaged as an individual choice that can be made at older ages, having a child after a certain age can be impossible -either “naturally” or using assisted reproductive technology-depending on the medical and legislative possibilities and limits of the country in which people live. In the extremely diverse European reproscape, reproductive legislations have forced but also allowed many people to seek reproductive treatments outside their home countries.Spain is a leading destination in Europe for cross border reproductive travel and, of the foreigners it receives, the French are the largest group. Despite having a history of strong pro-natalist policies, France has been one of the strictest European countries regarding access to medically assisted procreation. Until 2022, only heterosexual couples in which women were under 43 years of age could access treatments. Despite the recent opening of access to “all women”, including single women and same-sex female couples, women over 43 years of age were once again excluded from the new legal framework and therefore remain condemned to travel abroad to access reproductive treatments. In this article, we analyze the experience of French women over 40 who cross the Spanish border to access reproductive treatments in order to fulfill their desire to have children. Through ethnographic data emerging from six years of participant observation and in-depth interviews with 15 women, we explore why they remain excluded from the French system of reproductive governance and the obstacles they face during their reproductive journey.

Retracted Article: Analysis of Assisted Reproductive Technology Treatment of 126 Uterine Adenomyosis Patients Diagnosed via Ultrasonography

Background: Uterine Adenomyosis (Ut-Ad) is a condition in which the endometrial glands and stroma invade extensively into the uterine myometrium, causing the uterus to enlarge and leading to treatment-resistant infertility. In this study, we diagnosed Ut-Ad in the absence of concomitant ovarian endometriosis using ultrasound and conducted assisted reproductive technology (ART) on 126 patients desiring pregnancy. We report our clinical outcomes and discuss potential future treatments. Methods: Ut-Ad was diagnosed independently, without concurrent external endometriosis. We retrospectively analyzed the clinical pregnancy, live birth, and miscarriage rates of 126 patients with Ut-Ad who underwent ART at our clinic, comparing them with 2,472 non-Ut-Ad individuals as controls. Additionally, we examined CA-125 levels and assessed the severity of dysmenorrhea. Results: The Ut-Ad group exhibited significantly lower pregnancy and live birth rates, along with lower gestational age and birth weight, compared to the non-Ut-Ad group. However, embryonic development until embryo transfer was comparable between the Ut-Ad and non-Ut-Ad groups. Notably, the miscarriage rate in the Ut-Ad group was significantly higher than that in the control group. Conclusions: Historically, clinical outcomes for Ut-Ad have been suboptimal, even with the use of modern ART treatments, resulting in low pregnancy rates. While the exact cause of Ut-Ad remains elusive, recent ultrasound findings suggest that minor disruptions in the uterine endometrium may contribute to adenomyosis development in young women with symptoms. Continuous monitoring via transvaginal ultrasound could facilitate early diagnosis and treatment, potentially offering substantial benefits for Ut-Ad management in the future.

Human Umbilical Cord Mesenchymal Stem Cells Derived Exosomes Improved The Aged Mouse IVM Oocytes Quality.

During assisted reproductive technology (ART) treatment, the aged women, especially those over 35years old, have fewer mature oocytes and poorer quality of the oocytes comparing with the young women. In vitro maturation (IVM) technology facilitates the usage of immature oocytes, which is clinically important for the aged women. However, the maturation rate is low for the oocytes from the aged women. Human umbilical cord mesenchymal stem cells derived exosomes (HUCMSCs-exosomes), as important mediators of intercellular communication, have been widely used to restore ovarian function and improve female fertility. In this study, we isolated HUCMSCs-exosomes and collected the immature germinal vesicle oocytes from the naturally aged mouse model. And we added these HUCMSCs-exosomes to the conventional IVM culture system. The effects of HUCMSCs-exosomes on IVM oocytes were observed and analyzed from multiple aspects including maturation rate, spindle morphology, mitochondria function, and development potential. We found the quality of oocytes was improved by HUCMSCs-exosomes. Based on the results, we propose that HUCMSCs-exosomes may provide a novel and cell free strategy in the improvement of the IVM in elderly infertile women in the future.

Urinary haloacetic acid concentrations and thyroid function among women: Results from the TREE study

BackgroundDisinfection byproducts (DBPs) have been shown to impair thyroid function in experimental models. However, epidemiological evidence is scarce. MethodsThis study included 1190 women undergoing assisted reproductive technology (ART) treatment from the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. Serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured as indicators of thyroid function. FT4/FT3 and TSH/FT4 ratios were calculated as markers of thyroid hormone homeostasis. Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the two most abundant HAAs, in urine were detected to assess individual DBP exposures. ResultsAfter adjusting for relevant covariates, positive associations were observed between urinary TCAA concentrations and serum TSH and TSH/FT4 levels (e.g., percent change = 5.82 %, 95 % CI: 0.70 %, 11.21 % for TSH), whereas inverse associations were found for serum FT3 and FT4 (e.g., percent change = −1.29 %, 95 % CI: −2.49 %, −0.07 % for FT3). There also was a negative association between urinary DCAA concentration and serum FT4/FT3 (percent change = −2.49 %, 95 % CI: −4.71 %, −0.23 %). These associations were further confirmed in the restricted cubic spline and generalized additive models with linear or U-shaped dose-response relationships. ConclusionUrinary HAAs were associated with altered thyroid hormone homeostasis among women undergoing ART treatment.

The Multi-faceted Effects of COVID-19 on Female Reproductive Health: An Updated Narrative Review.

Concerns about the SARS-CoV-2 pandemic's possible impact on sexual and reproductive health have grown significantly. In this narrative review, the latest research on the effects of SARS-CoV-2 infection on several facets of sexual and reproductive health is reviewed. The review starts initially by going through thepossible consequences of SARS-CoV-2 on female menstrual cycles. The virus may interfere with the menstrual cycle, which could affect hormone synthesis and endometrial reactions, according to newly available evidence. Menstrual blood loss may be impacted by COVID-19's potential to influence endothelial cell function and systemic hemostasis. Hypothalamic amenorrhea may be brought on by severe COVID-19 disease. There is little research on this subject, although most women resume their regular menstrual cycles after 1-2 months of recuperation. The review also examines how SARS-CoV-2 infection may affect assisted reproductive technology (ART) treatments. There are few clinical data, although some research points to potential effects on embryo quality. Overall, ART results, however, did not materially change from the time before the epidemic. Obstetric problems are more likely when SARS-CoV-2 infection occurs during pregnancy, especially in the third trimester. Even though the maternal death rate is still low, pregnant women, especially those with comorbidities, are more likely to experience serious sickness. The review emphasizes how the COVID-19 vaccine affects menstrual cycles, showing brief, modest modifications without serious health hazards. Also included are the psychological effects of family planning choices during the pandemic. In conclusion, this narrative review offers a thorough assessment of the complicated and changing effects of SARS-CoV-2 on sexual and reproductive health. The different requirements of people and couples during and after the pandemic are highlighted, underscoring the necessity for ongoing study and specialized healthcare practices.

Is Endometrial Receptivity Affected in Women With Endometriosis? Results From a Matched Pair Case-Control Study of Assisted Reproductive Technology Treatments

(Abstracted from Reprod Biomed Online 2023;47:103414 Endometriosis is a well-established risk factor for infertility due to alterations in folliculogenesis, oocyte release from the ovaries, tubal function, and oocyte fertilization. In addition, it has been hypothesized that the presence of an abnormal endometrium, a known consequence of endometriosis, may impair embryo implantation leading to impaired pregnancy outcomes.