Assisted Reproduction Treatment Outcome Research Articles

Association Between Vitamin D Level and Clinical Outcomes of Assisted Reproductive Treatment: A Systematic Review and Dose-Response Meta-Analysis.

The investigation about association between vitamin D level and clinical outcomes of assisted reproductive treatment showed various outcomes. This study aimed to review the correlation between vitamin D and outcomes of assisted reproductive treatment. The search was registered on the PROSPERO database (CRD42023458040). PubMed, Embase, Medline, ClinicalTrials.gov, and Cochrane databases were searched up to July 2023. Twenty-three observational studies were selected for meta-analysis. Comparing groups with deficient and 'insufficient + sufficient' vitamin D level, meta-analysis showed positive correlation between clinical pregnancy rate and vitamin D (OR 0.81, 95%CI: 0.70, 0.95, P = 0.0001). Comparing groups with 'deficient + insufficient' and sufficient vitamin D level, meta-analysis showed positive correlation between vitamin D and clinical pregnancy rate (OR 0.71, 95%CI: 0.55, 0.91, P = 0.006), vitamin D and live birth rate (OR 0.69, 95%CI: 0.54, 0.89, P = 0.003). Subgroup analysis did not show the source of high heterogeneity. No correlation was found in biochemical pregnancy rate, ongoing pregnancy rate, miscarriage rate and implantation rate. In dose-response meta-analysis, a nonlinear association was found between vitamin D levels and outcomes when levels are below approximately 24 ng/L. The study shows that vitamin D level is associated with clinical pregnancy rate and live birth rate. Low vitamin D level does not influence biochemical pregnancy rate, ongoing pregnancy rate, miscarriage rate and implantation rate. Furthermore, 24 ng/L may be a possible threshold of vitamin D concentration in assisted reproduction therapy.

The impact and inflammatory characteristics of SARS-CoV-2 infection during ovarian stimulation on the outcomes of assisted reproductive treatment.

Despite the global prevalence of coronavirus disease 2019 (COVID-19), limited research has been conducted on the effects of SARS-CoV-2 infection on human reproduction. The aims of this study were to investigate the impact of SARS-CoV-2 infection during controlled ovarian stimulation (COS) on the outcomes of assisted reproductive treatment (ART) and the cytokine status of patients. This retrospective cohort study included 202 couples who received ART treatment, 101 couples infected with SARS-CoV-2 during COS and 101 matched uninfected couples. The parameters of ovarian stimulation and pregnancy outcomes were compared between the two groups. The All-Human Inflammation Array Q3 kit was utilized to measure cytokine levels in both blood and follicular fluid. No difference was found in the number of good-quality embryos (3.3 ± 3.1 vs. 3.0 ± 2.2, P = 0.553) between the infected and uninfected groups. Among couples who received fresh embryo transfers, no difference was observed in clinical pregnancy rate (53.3% vs. 51.5%, P = 0.907). The rates of fertilization, implantation, miscarriage, ectopic pregnancy and live birth were also comparable between the two groups. After adjustments were made for confounders, regression models indicated that the quality of embryos (B = 0.16, P = 0.605) and clinical pregnancy rate (P = 0.206) remained unaffected by SARS-CoV-2 infection. The serum levels of MCP-1, TIMP-1, I-309, TNF-RI and TNF-RII were increased, while that of eotaxin-2 was decreased in COVID-19 patients. No significant difference was found in the levels of cytokines in follicular fluid between the two groups. Asymptomatic or mild COVID-19 during COS had no adverse effects on ART outcomes. Although mild inflammation was present in the serum, it was not detected in the follicular fluid of these patients. The subsequent immune response needs further investigation.

Sperm selection by zona adhesion improves assisted reproductive treatment outcomes.

Zona pellucida is one of the main selective barriers for the spermatozoa before reaching the oocyte. Using native zona in the sperm selection prior to Intracytoplasmic Sperm Injection (ICSI) has been proven effective but inconvenient approach in In Vitro Fertilisation (IVF) laboratory. The application of autologous solubilised zonae pellucidae in the sperm selection prior to ICSI has not been studied yet. To compare the assisted reproductive treatment (ART) outcomes (implantation, pregnancy, live birth, and miscarriage rates) after ICSI performed with spermatozoa selected on their ability to adhere to immobilised solubilised zonae pellucidae and conventionally selected spermatozoa. In total, 500 couples fulfilled the inclusion criteria and 368 of them were included in the study. After random allocation, 192 couples had spermatozoa selected by sperm-zona adhesion for ICSI (study group) and 176 patients underwent standard ICSI (control group). In the study group, patients' own zonae were acid solubilised and immobilised on petri dishes. The partner's motile spermatozoa were placed in the dishes and the adhered spermatozoa were used for ICSI. For the control group, the conventional sperm selection by morphological criteria was applied prior ICSI. All women underwent frozen ET with euploid embryos. Chi square test was used to compare the data. The sperm selection by zona adhesion resulted in significantly higher implantation rate (50.4%vs. 37.0%, p=0.003), clinical pregnancy rate (43.8%vs. 33.3%, p=0.018) and live birth rate (38.0%vs. 25.9%, p=0.004) and significantly lower incidence of miscarriage (11.3%vs. 22.2%, p=0.044) in comparison to the conventional method of the sperm selection. The application of solubilised zonae pellucidae in the sperm selection for ICSI benefits ART outcomes in couples with unexplained infertility. Moreover, sperm-zona selection significantly reduces the risk of miscarriages.

P-175 Human cumulus cell telomere length and its association with assisted reproduction outcomes

Abstract Study question Is there any relationship between the relative telomere length (RTL) within cumulus cells (CCs) and the outcome of assisted reproductive treatment using the corresponding oocyte? Summary answer Lower RTLs in CCs were significantly associated with embryos chosen for transfer or cryopreservation. In contrast, embryos considered non-viable (discarded) tended to have higher RTLs. What is known already Cumulus cells fulfil vital roles in support of oocyte development, including the transduction of external signals and the provision of resources via transzonal projections. Given their essential role in the acquisition of oocyte developmental competence, the biology of CCs is of clinical relevance. Telomeres are specialised structures protecting the ends of chromosomes, composed of repetitive DNA sequences and associated proteins. Telomeres shorten with each mitotic division, as well as due to oxidative damage, eventually reaching a critical threshold at which point cellular senescence occurs. Currently, published data on CCs telomere length and relationship with oocyte potential are conflicting. Study design, size, duration The study involved 182 human CC samples collected from 52 IVF patients. Quantitative PCR (qPCR) was used to measure the relative telomere length in each of the CC samples. Telomere lengths were assessed for associations with various patient characteristics (e.g. age, body mass index, infertility diagnosis). Additionally, potential relationships with clinically relevant oocyte/embryo features were investigated (fertilisation; development/morphology), as well as the eventual fate of the associated embryo (transferred; cryopreserved for potential future use; discarded). Participants/materials, setting, methods Real-time quantitative PCR was carried out using PCR primers specific for the telomere repeat. A single-copy gene was also amplified from each CC sample. Quantification of this gene was used for normalisation of the telomere data, allowing control for variation in the number of cumulus cells in each sample. Associations between RTL in CCs and patient, embryonic, and clinical factors were assessed using various statistical methods, with P-values <0.05 considered significant. Main results and the role of chance No associations were identified between RTL and any patient characteristics, except for BMI. The amount of CC telomeric DNA tended to be greater for patients with higher BMI (P = 0.002). When considering links between RTL and oocyte or embryonic factors, a significant relationship was detected between the quantity of telomeric DNA in CCs and whether the corresponding embryo was considered non-viable (discarded) or whether it was transferred or cryopreserved (P = 0.019). This finding raises the possibility that measurement of RTL in CCs could provide a pre-conception, non-invasive assessment of oocyte quality. In the context of fertility preservation, RTL measurement could assist in evaluating a cohort of oocytes, indicating whether the cryopreserved eggs are likely to be sufficient or whether additional cycles to generate more would be advisable. If future studies confirm that CC RTL has a strong predictive value, the possibility of limiting fertilisation to oocytes considered to have high likelihood of viability could also be considered for routine IVF cycles. It is unclear why shorter CC telomeres might be associated with oocytes of superior potential, but one possibility is that the cells may have undergone a greater proliferation (more mitoses), resulting in a more extensive cumulus mass supporting the enclosed oocyte. Limitations, reasons for caution Before drawing definitive conclusions, confirmation of the findings within a larger, independent data set is necessary. Even if confirmed, determination of the true clinical value of telomere assessment will require further, appropriately designed studies. The current study was not powered to evaluate relationships between CC telomere lengths and IVF outcomes. Wider implications of the findings Currently, simplistic morphological evaluation is the only method for assessing oocyte competence prior to fertilisation. If CCs telomere measurement is confirmed to have predictive value, a preconception test of oocyte potential could be offered. This would be extremely valuable for patients cryopreserving oocytes for fertility preservation and for donor banks. Trial registration number NA

Genital Microbiota and Outcome of Assisted Reproductive Treatment-A Systematic Review.

The balance between different bacterial species is essential for optimal vaginal health. Microbiome includes the host genome along with microorganism genomes and incorporates the biotic and abiotic factors, reflecting the habitat as a whole. A significant difference exists in the composition and number of the human microbiota in healthy individuals. About one-tenth of the total body microbiota exists in the urogenital tract and these can be identified by microscopy and culture-based methods, quantitative PCR, next generation and whole genome sequencing. The trend of delaying the planning of pregnancy to a later age nowadays has resulted in magnifying the use of assisted reproductive treatment (ART). Hence, genital microbiota and its impact on fertility has generated immense interest in recent years. In this systematic review, we searched the available evidence on the microbiota of the genital tract in women undergoing ART and studied the outcomes of IVF in different microbial compositions. Despite the inconsistency of the studies, it is evident that vaginal, cervical and endometrial microbiota might play a role in predicting ART outcomes. However, there is no clear evidence yet on whether the diversity, richness, quantity, or composition of species in the maternal genital tract significantly affects the outcomes in ARTs.

RACIAL DISPARITY IN HEALTHCARE EXPERIENCE AMONG PATIENTS SEEKING FERTILITY CARE DURING THE COVID-19 PANDEMIC

Recent data have shown that there are racial disparities in access and outcomes of assisted reproductive technology treatment in the USA (1), however, the effect of the pandemic on this racial disparity has not been studied. Thus, the primary aim of this study was to identify how the pandemic has affected patient decision-making regarding fertility planning and treatment among black versus non-black women. Following IRB approval, a link to a survey was sent to the emails of all patients presenting to a university-affiliated fertility clinic between January 2021 and December 2021. The patients were asked to fill out a questionnaire regarding fertility plans prior and during the pandemic. Data collected included demographics about age, race, ethnicity, employment, vaccination, fertility treatments prior to the pandemic and changes in treatments during the pandemic. Data are presented as percentages and chi-square test was performed for statistical analysis. A total of 223 patients (mean age 41 ± 1.6) filled out the questionnaire. When all participants were asked about fertility treatment plans before the pandemic, 58% were pursuing IVF, 7% wanted oocyte freezing, 4% wanted IUI, and 31% were doing fertility work-up. The majority (69%) reported that the pandemic did not change their plans and the minority reported either postponing or canceling their treatments with financial instability being the most commonly reported reason (22%). Fewer black women were vaccinated compared to non-black women (35% vs. 52%; p=0.03). When asked whether the pandemic was well-handled by major healthcare systems, black women were less likely to think that it met expectations compared to non-black women (35% vs. 54%; p=0.02). Additionally, black women were less likely to be uncomfortable visiting the office in person during the pandemic compared to non-black women (2% vs. 15%; p=0.02). Interestingly, there was no difference between black and non-black women when asked whether they think that the vaccine could affect fertility or pregnancy outcomes or whether taking the vaccine stopped them from pursuing fertility treatments (p>0.05). Among women undergoing fertility treatments during the pandemic, black race was associated with less likelihood of being vaccinated, less likelihood of being satisfied with major healthcare systems handling the pandemic, and more comfort in visiting physically the fertility clinic.

Evaluation of assisted reproductive technology treatment outcomes based on stimulation dosages and anti-Mullerian hormone levels

Background: Serum levels of anti-Müllerian hormone (AMH) have a significant association with ovarian response in the event of assisted reproductive technology (ART) treatment cycles. The present study was performed to evaluate the ovarian stimulation protocols selection with respect to serum AMH levels in patients and its impact on ART outcome. Methods: Based on the serum AMH, 191 women were classified as low, normal and high responders. Follicle Stimulating Hormone (FSH) and Human Menopausal Gonadotropin (HMG) dosages in controlled ovarian stimulation were determined. Retrieval, maturation, fertilization and utilization rates were measured. Subgroup analysis was done using one-way ANOVA followed by post hoc analysis. The relationship between AMH levels and fertilization was determined using Pearson’s correlation analysis. A p-value <0.05 was considered as statistically significant. Results: According to AMH levels, the majority of the patients were normal responders (52.4%) followed by high responders (29.8%) and low responders (17.8%). The average FSH, HMG per day and number of days HMG required was found to be significant among the different responders. Further, retrieval rate and blastulation rate was found to be significant among the different responders. A positive correlation was found between AMH and the number of oocytes retrieved and number of oocytes successfully fertilized, which was found to be significant. In addition, there was a significant inverse relationship between AMH levels and age. Conclusions: The study outcomes revealed that the rates of retrieval, maturation, fertilization, embryo utilization and blastulation were higher among the high responders compared with the low responders. Thus, proper increase in dosages of ovarian stimulation protocol is required among the low responders to achieve quality embryos.

The relationship between coping strategies and infertility self-efficacy with pregnancy outcomes of women undergoing in vitro fertilization: A prospective cohort study.

BackgroundAssisted reproductive technology treatments are stressful procedures, but there are individual differences in the emotional response to them. Differences in response to this stress may be related to the outcome of infertility treatment.ObjectiveThis study aimed to investigate the relationship between coping strategies and infertility self-efficacy with pregnancy outcomes of women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment.Materials and MethodsThis was a prospective cohort study and the 154 infertile women were psychologically evaluated in 2 stages: once before ovarian stimulation and again during embryo transfer. The research measurements used were the Revised COPE, the Depression Anxiety Stress Scale (DASS-21) and the Infertility Self-Efficacy Scale.ResultsThere was no significant difference between the group of non-pregnant women and the positive pregnancy group in terms of coping strategies (mental rumination, self-blame, active confronting, goal replacement, avoidance) or self-efficacy in either of the 2 stages of ovarian stimulation and embryo transfer. The Mann-Whitney test did not show any statistical difference between the clinically pregnant women and the only laboratory positive pregnant group. Moreover, the self-blame and mental rumination strategies were positively related with anxiety and depression. Conversely, active confronting, goal replacement, avoidance and self-efficacy were associated with decreased depression, anxiety and stress levels.ConclusionIt can be concluded that there is no relationship between coping strategies and infertility self-efficacy with in vitro fertilization/intracytoplasmic sperm injection outcomes. Further research is needed to clarify the effects of other psychological factors on the pregnancy outcomes of assisted reproductive treatment.

Effect of metformin and exenatide on pregnancy rate and pregnancy outcomes in overweight or obese infertility PCOS women: long-term follow-up of an RCT.

The majority of Polycystic ovary syndrome (PCOS) are overweight or obese with increased infertility and high risk of pregnancy complications. We aim to compare efficacy of metformin and exenatide on spontaneous pregnancy rate, overall pregnancy rate after assisted reproductive technology treatment (ART) and pregnancy outcomes in overweight or obese infertility PCOS. In this long-term follow-up study, 160 overweight or obese infertility Chinese PCOS were randomized to exenatide or metformin treatment for 12weeks. Afterward, all were treated with metformin alone until pregnancy confirmed and followed until delivery. If patients failed spontaneous pregnancy during the second 12weeks, ART could be offered until end of 64weeks. The primary outcome was spontaneous pregnancy rate. At week 24, 29.2% of women in exenatide group conceived spontaneously while 14.7% in metformin group (p = 0.03). At week 64, total pregnancy rates were 79.2% in exenatide group and 76% in metformin group without significant difference (p = 0.65). Between two groups, there was no significant difference of pregnancy outcomes (p > 0.05). A stepwise logistic regression showed that spontaneous pregnancy was positively associated with body weight reduction and HOMA-IR improvement in either group. In overweight or obese infertility Chinese PCOS, 12weeks pregestational exenatide treatment resulted in more spontaneous pregnancy likely due to greater weight reduction and improvement of insulin resistance compared with metformin treatment without obvious benefit on overall pregnancy rate after ART or pregnancy outcomes of successful conceived women. This clinical trial was registered at Chinese Clinical Trials Registry (ChiCTR-IIR-16008084) on 13/3/2016.

Impact of paternal body mass index on assisted reproduction treatment outcomes: An updated systematic review and meta-analysis.

The aim was to provide updated evidence on the association of male body mass index (BMI) with outcomes of assisted reproduction technology (ART). PubMed, Embase, and Scopus databases were systematically searched. The review included observational studies in patients undergoing ART, that is, either in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and compared rate of clinical pregnancy and live birth based on different categories of male BMI. Quality of the pooled findings was assessed using the GRADE criteria. A total of 19 studies were included in the review. Among subjects undergoing IVF, there were no significant differences in the rates of clinical pregnancy among overweight (odds ratio [OR] 1.38, 95% confidence interval [CI]: 0.65, 2.96) and obese (OR 1.86, 95% CI: 0.75, 4.58) BMI, compared to normal male BMI. Similarly, there were no significant differences in the rates of live birth among overweight (OR 1.04, 95% CI: 0.97, 1.13) and obese BMI (OR 0.90, 95% CI: 0.69, 1.18) when compared to males with normal BMI. Further, among those undergoing ICSI, there were no significant differences in the odds of clinical pregnancy among overweight (OR 0.98, 95% CI: 0.73, 1.33) and obese (OR 0.89, 95% CI: 0.62, 1.29). The odds of live births among overweight (OR 0.97, 95% CI: 0.89, 1.05) and obese (OR 0.95, 95% CI: 0.84, 1.07) male BMI were statistically similar to males with normal BMI undergoing ICSI. The low to very low-quality findings suggest no significant association of overweight and obese BMI with clinical pregnancy and live birth rates among couples undergoing either IVF or ICSI.

Female obesity: Association with endocrine disruption and reproductive dysfunction

Obesity affects female fertility and fecundity through a complex set of mechanisms involving an imbalance of hormones, changes in the adipose tissue, reproductive system, adipokines, cytokines, metabolic perturbation, dysbiosis, and ovulatory and embryonic malfunction. Obesity is an important factor for hyperandrogenism, hyperinsulinemia, and the development of polycystic ovarian syndrome (PCOS). PCOS impairs the functioning of gut microbes which in turn interrupts inflammatory signaling in the hypothalamic-pituitary-gonadal (HPG) axis and oocyte development. It causes abnormalities in the reproductive cycle, an increase in the body mass index (BMI), and alters the outcome of assisted reproductive treatment. Furthermore, kisspeptin-dependent leptin pathways augment the regulation of gonadal releasing hormone (GnRH) secretion to maintain ovarian function. The level of ghrelin and leptin is associated with the onset of puberty and inflammatory factors, mainly tumor necrosis factor (TNF)-α and interleukin (IL)-6. These affect the fertility of females by exacerbating oocyte development, insulin resistance, and PCOS. This article highlights the effect of obesity on the female reproductive system with the involvement of the interaction of various hormones, binding protein, inflammatory agents, metabolic perturbation, dysbiosis, obesity-induced alteration in the hypothalamic-pituitary-ovarian (HPO) axis and sustainable goals to manage obesity. • Infertility biomarker in obese women is irregularity in menses, miscarriages, and hormonal imbalance. • Insulin signaling impairment in reproductive axis results development of polycystic ovarian syndrome. • The impaired interaction of adipokines and inflammatory factor with reproductive axis negatively affects reproductive potential.

Anorexigenic peptide (leptin, obestatin, nesfatin-1) levels and their impact on assisted reproductive technology treatment outcomes in patients with polycystic ovary syndrome.

ObjectiveIn this study we aimed to assess anorexigenic peptide levels in patients with or without polycystic ovary syndrome (PCOS) and their effects on assisted reproductive treatment (ART) outcomes.MethodsA prospective case-control study was conducted in a tertiary care university-based ART clinic. Eighty-three patients were included in the study. The PCOS group included 41 patients, and the non-PCOS group included 42 controls. The 2003 Rotterdam criteria were used for PCOS patient selection. The ART indications in the non-PCOS group were tubal factor or unexplained infertility. Venous blood samples were taken on the third day of the menstrual cycle to determine the serum anorexigenic peptide levels. The enzyme-linked immunosorbent assay method was used for laboratory analyses.ResultsIn the PCOS group, serum obestatin levels were significantly lower than in the control group, but serum anorexigenic peptide levels were similar in PCOS patients with or without clinical pregnancy. Ovarian hyperstimulation syndrome (OHSS) was diagnosed only in PCOS patients, and the obestatin levels of OHSS patients were significantly lower than those of other PCOS patients.ConclusionsBaseline anorexigenic peptide levels did not affect the clinical pregnancy rate in ART cycles. Obestatin may play a role in the pathophysiology of OHSS. This possibility should be confirmed in further research.

Effect of bariatric surgery on invitro fertilization in infertile men with obesity.

Obesity has previously been related to reduced female fertility, with prolonged waiting time to pregnancy among women with a body mass index (BMI) >35 kg/m2 but there are few studies investigating the relationship between high BMI, bariatric surgery, and male fertility. The primary objective of this article was to investigate the effect of bariatric surgery on invitro fertilization (IVF) outcomes in a cohort of men with morbid obesity who underwent sleeve gastrectomy (SG). University hospital, bariatric surgery unit. Pre- and postsurgery data on patient age, body mass index (BMI), and variables related to male fertility (semen volume, concentration, progressively motile sperm count, and sperm morphology) were collected; assisted reproductive technology outcomes before and after bariatric surgery were measured by the number of metaphase II oocytes; the number of top-quality oocytes and embryos; the number of fertilized oocytes; the number of transferred embryo; the implantation rate; the pregnancy rate; the live birth rate and the miscarriage rate. Thirty-five men with obesity and idiopathic infertility were included in this study. We found a significant increase, after bariatric surgery, in semen volume, total sperm concentration, progressively motile sperm count, and sperm morphology. Considering IVF outcomes, mean number of top-quality oocytes, mean number of fertilized oocytes, mean number of embryos obtained, and top-quality embryos were significantly increased after bariatric procedure. Bariatric surgery is confirmed to be safe and effective in increasing the outcomes of assisted reproductive technology treatment also in case of infertile men with obesity, both in terms of pregnancy and live birth rate.

Sperm morphology and DNA fragmentation after zona pellucida selection.

Sperm DNA fragmentation (SDF) and sperm morphological defects can negatively affect ART outcomes. Consequently, there is a need for additional semen processing technique that accounts for sperm DNA status and morphology prior to ICSI. The objective was to evaluate the efficacy of an additional zona pellucida adhesion-based sperm selection for obtaining sperm populations with a high percentage of normal morphology and DNA integrity as compared to native semen and routine swim-up preparation. Semen samples from 78 normozoospermic men were subjected to swim up and placed in petri dishes coated with 48 acid-solubilized zonae pellucidae. Sperm DNA fragmentation and morphology were assessed in the native semen, the swim-up samples, and the zona-adhered spermatozoa from each patient. The mean sperm DNA fragmentation of the zona-selected spermatozoa (3.5 ± 0.7%) was significantly lower than the swim-up samples (15.3 ± 5.2%) (P < 0.001) and native semen (24.9 ± 7.1%) (P < 0.001). All of the samples had lower levels of DNA damage after additional selection by zona pellucida adhesion. Significantly higher percentage of sperm with normal morphology was observed after zona-adhesion selection (11.4 ± 3.9%) when compared to the swim-up samples (8.9 ± 4.3%) (P < 0.001) or the native semen (5.3 ± 3.2%) (P < 0.001). In 94% of the samples, the percentage of spermatozoa with normal morphology increased after the additional zona selection. This study demonstrates that sperm selection by additional zona-adhesion technique yields a significantly higher percentage of spermatozoa with normal morphology as well as a significantly decreased level of DNA fragmentation when compared to the native semen and the swim-up-only prepared samples.Lay summaryHigh level of DNA folding known as sperm DNA fragmentation (SDF) inside each sperm and defects in the shape, size, and structure of the sperm can negatively affect assisted reproduction treatment (ART) outcomes. Consequently, there is a need for additional semen processing techniques that account for sperm quality prior to ART. Our team designed a simple technique using proteins from the coat around the egg (zona pellucida) to enhance sperm selection procedures based on natural sperm–egg interactions. Using this technique in combination with the most common techniques used in ART yields a significantly higher percentage of sperm with normal shape, size, and structure and a decreased level of DNA fragmentation. This sperm zona-selection technique would be beneficial if introduced in the ART practice to yield sperm with higher fertilization potential.

P–729 Seasonality and lunar phase impact zona pellucida thickness while assisted reproductive treatment outcome shown no differences between seasons

Abstract Study question Does seasonal variation impact zona pellucida (ZP) thickness, other assisted reproductive treatment (ART) factors and ART outcome? Summary answer Seasonality and lunar phase impact ZP thickness while specific weather conditions alone do not, however, seasonality does not impact other ART factors or ART outcome. What is known already: Several epidemiological studies have demonstrated seasonal variation in natural pregnancy and birth rate, which varies across geographic regions. It has been suggested that temperature and light may affect the ability to conception via hormonal changes. However, data regarding the seasonal variation during ART is controversial and several studies with conflicting results have been published. One retrospective observational cohort study reported the significant influence of seasonality on fertilization rates with highest ones during the spring and the lowest ones in the autumn. However, another retrospective study did not demonstrate any significant influence of the seasons on ART outcome. Study design, size, duration This retrospective study was performed in the Fertility Center, VUH Santaros Clinics, Lithuania. 959 IVF/ICSI cycles conducted in IVF laboratory between 2017 and 2019 were analysed. The thickness of ZP was measured of 5002 oocytes retrieved between 2017 and 2018. Degenerated oocytes were excluded from the study. Average temperature (AT), precipitation (AP) and sunshine hours (ASH) of every month were taken from Lithuanian Hydrometeorological Service database. Lunar phase (LP) data was collected using Google Calendar. Participants/materials, setting, methods IVF/ICSI cycles were divided into four seasonal groups according to the day of oocyte pick-up. The number of retrieved and fertilized oocytes, transferred embryos, fertilization and pregnancy rates were compared among groups. Then, to avoid bias in fertilization rate, ICSI cycles were excluded and only IVF cycles were analysed. Measurements of ZP thickness were taken using NIS-Elements F software. It was evaluated if AT, AP, ASH, LP and seasonality had an effect on ZP thickness. Main results and the role of chance The mean number of retrieved oocytes and fertilized oocytes as well as the percentage of women who conceived was highest in the spring and lowest in the summer without statistical significance among all seasonal groups (p &amp;gt; 0.05). The fertilization rate was lowest in the spring (66.60%) and highest in the autumn (68.76%) without statistical significance among all four groups. The odds were 1.49 times higher to conceive in spring compared to summer and this result was statistically significant (95% CI 1.01–2.21; p = 0.046), however, when comparing all four seasons together, the difference was not significant. The calculations with only IVF cycles followed the same pattern except that the odds ratio results were not significant and the fertilization rate was highest in the winter. None of the weather conditions (average temperature, average precipitation and average sunshine hours) had an impact on ZP thickness. However, the mean ZP thickness was lowest in the summer (18.86 ± 3.08 µm) and highest in the autumn (19.43 ± 2.98 µm) and the difference among all four seasons was statistically significant (p &amp;lt; 0.05). The mean ZP thickness was lowest during the first quarter lunar phase and highest during the new moon phase with statistical significance among groups (p &amp;lt; 0.05). Limitations, reasons for caution A limitation of our study is unequal number of the IVF/ICSI procedures between months/seasons (e.g., the sample size of autumn was 340 while the sample size of summer was only 161). Also, the measurements of ZP were taken manually therefore there could be some errors. Wider implications of the findings: Understanding possible effects of external factors on ART outcome is important for the best treatment results. Even though seasonality and lunar phase significantly impact ZP thickness, we could not demonstrate any significant seasonal influence on other ART factors or ART outcome. Further studies with higher number of patients are required. Trial registration number Not applicable

Antiphospholipid antibodies and pregnancy outcome of assisted reproductive treatment: A systematic review and meta-analysis.

Antiphospholipid antibodies (aPLs) are a group of autoantibodies associated with a variety of pregnancy complications, but the impact of aPL on the outcomes of assisted fertility treatment (ART) is controversial. This systematic review and meta-analysis were designed to explore the association between aPL and ART outcomes and to explore in which stages does aPL play a role. PubMed and Cochrane database were systematically retrieved, and odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CIs) were calculated in a random-effect model or fixed-effect model according to the heterogenicity assessed by the Cochran Q and I2 statistic test. Of 246 records identified by the search, 10 case-control studies and 13 cohort studies that explored the association between aPL and in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) were analyzed. The results showed that aPL positive rate was higher in females who failed in IVF/ICSI than those who succeeded in IVF/ICSI (OR: 3.62, 95% CI: 1.95-6.74). This study also indicated that females positive for aPL have a higher miscarriage rate (RR: 1.68, 95% CI: 1.24-2.28) than those negative for aPL, but live birth rate, biochemical pregnancy rate, and clinical pregnancy rate were similar between two groups (RR: 1.01, 95% CI: 0.91-1.12; RR: 1.18, 95% CI: 0.57-2.43 and RR: 0.95, 95% CI: 0.80-1.13). There was higher aPL prevalence in females with adverse IVF/ICSI outcomes. It seems that aPL mainly affects the miscarriage rate, but has little effect on live birth rate, biochemical pregnancy rate, and clinical pregnancy rate. Routine detection of aPL before IVF/ICSI treatment is meaningful.

Sleep, cosmetic skin treatments and assisted reproduction in advanced age women: A possible triad of interaction

There is a growing trend among women to postpone motherhood for several reasons, although fertility decreases with age.1, 2 Women over 35 years old, considered as advanced maternal age, can benefit from assisted reproductive treatment (ART), which is making an increasing contribution to birthrates worldwide.2 According to recent data (REDLARA), 72.2% of women who underwent ART in 2017 were over 35 years.2 Despite successful rates of ART, pregnancies in women of advanced age have higher risks of failure, maternal and foetal complications,1, 2 requiring even more caution in their care. This includes paying attention to the sleep quality, as sleep is important to the regulation of the organism. Women undergoing ART may have poor sleep quality3 that may impair fertilization and hormonal management. Simultaneously, they may have greater concerns about their self-image due to ageing and deprived sleep,4, 5 which could increase their demand for skin procedures. The risks of these procedures to ART are still not clear, requiring further investigation. We raise possible effects of dermatological treatments during ART and the role of sleep in this interaction. Sleep could be a link between skin ageing, the necessity of skin treatment, and ART, as sleep acts in both hormonal and oxidative stress (OS) regulation (References S1 and S2). Poor sleep quality, especially due to increased OS, can accelerate skin ageing (References S1 and S2). Parallelly, it could influence fertilization and ART outcomes. Sleep disturbance can result from the continuous psychological stress and anxiety of many women undergoing ART.3 Satisfactory sleep quality may be an important factor to ART success,3 given that reproductive endocrinological regulation could be affected by sleep distress.3 Chronic sleep dysregulation and harmful environmental exposure can increase OS,1 (Reference S1) which may also be greater across ageing and impair skin (References S1 and S2). Oxidative stress may impact skin appearance and fertility, with sleep being the main axis of this triad. Free radicals and OS may accelerate skin ageing due to cutaneous cell injury and affect fertility processes impacting ART,1 (Reference S1). Oxidative stress has been reported to produce abnormalities in the ovaries, impair embryo implantation and pregnancy success due to endothelial dysfunction.1 Oxidative stress (enhanced by poor sleep) can affect skin integrity (Reference S1 and S2), while satisfactory sleep is associated with healthy skin and hormonal balance (Reference S1). Adrenergic systems are boosted by prolonged stress, enhanced by poor sleep; this may accelerate skin ageing through immune and endocrinological impairment, higher OS and DNA injury (References S1 and S2), and may affect fertility.1 This three-way relationship may be significant in advanced age women. As an increasing number of women seeking ART are of advanced maternal age,2 part of these women could be using treatments to delay skin ageing and improve self-image (References S3 and S4), including periodic skin cosmetics and dermatological procedures (injectables and laser; References S3 and S4). Some products, such as chemical sunscreens, contain xenoestrogens, reported as possible factors that can influence fertility due to endocrine disruption (Reference S5). They may influence the hormonal regulation required for fertility success, especially in those suffering from poor sleep. Evidence has shown that good sleep quality is associated with a better perception of self-image,4, 5 (Reference S1). Better sleep, provided by sleep therapy, may help to delay skin damage through improved OS regulation, and minimize deleterious effects of OS on ART. Sleep therapy should be considered as important adjuvant care to women undergoing ART,3 as poor sleep can increase OS and hormonal imbalance (Reference S1). Retrospective studies examining ART outcomes in patients, skin treatment routines and sleep may provide initial base to this research line. Physicians should be encouraged to take a thorough clinical interview covering reproductive and dermatological areas, and sleep patterns. The possible risks and benefits of skin procedures must be considered. These measures could help to provide better assistance to these women by improving their life and sleep quality, and promoting successful ART outcomes. Our studies are supported by the Associação Fundo de Incentivo à Pesquisa (AFIP). MLA receives a CNPq fellowship. EMSX receives a CAPES Post-Graduate grant. No sponsorship was received for the publication of this manuscript. All authors declare no conflicts of interest. *AS and EMSX have contributed equally as first authors to the drafting, planning and writing of the manuscript. MS and MLA have contributed to conception and planning, major review and intellectual content of the work. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Stress and Anxiety Levels in Couples who Undergo Fertility Treatment: a Review of Systematic Reviews.

Background:Infertility is an issue that affects many parameters peoples’ lives, as individuals and as couples. Besides the physical and economic impact of infertility on the couples, there is a significant reflection of infertility on their mental health and well-being, which follows them from the moment of the diagnosis up until the end of their treatment.Objective:The aim of this review was to investigate whether psychological factors such as stress, anxiety or depression have an impact on the assisted reproduction treatment outcome and whether the use of supporting methods may help couples to minimize their fertility related stress, anxiety and depression and improve the treatment outcome.Methods:After a systematic search of the electronic databases, fourteen studies were included in this umbrella review. The included studies were systematic reviews and meta-analyses published between January 2015 and February 2020. The population of interest was women, men or couples facing infertility and undergoing fertility treatment. The included studies assessed the relationship between stress and anxiety in couples undergoing fertility treatment and the outcome of the treatment, the psychological state and psychological adjustment of the couples after a negative result and the impact of interventional methods for reducing stress, anxiety or depression on the psychological state of the couples undergoing treatment and their pregnancy outcomes.Results:This review fails to provide a certain answer to our research hypothesis due to conflicting results in the included studies. However, it has been observed that couples who reported better psychological state or have been treated with an interventional method for psychological support, were more likely to adjust better to the treatment procedure and the outcome as well.Conclusion:Psychological support and consultation during assisted reproduction treatment is highly recommended by researchers and clinicians.

How Are They Doing? Neurodevelopmental Outcomes at School Age of Children Born Following Assisted Reproductive Treatments

The purpose of this study was to assess major neurodevelopmental aspects of children conceived by assisted reproductive treatments compared to spontaneously conceived children during the early school years. In this follow-up study, mothers of 358 children born following assisted reproductive treatments and 401 spontaneously-conceived children were interviewed by telephone regarding their children's health and development, when the children were 7-8 years old. The main outcomes were maternal responses to 4 questionnaires: Developmental Coordination Disorder Questionnaire, Short Sensory Profile, Autism Spectrum Screening Questionnaire, and the Attention-deficit hyperactive disorder (ADHD) Child Symptom Inventory-4 subscale. Mothers reported diagnoses of ADHD and autism spectrum disorder. No significant differences were found between the groups in Developmental Coordination Disorder Questionnaire or Short Sensory Profile scores upon univariate or multivariable analyses. There was a slightly higher but nonsignificant rate of diagnosed ADHD among children in the assisted reproductive treatment group (9.6% vs 5.5%; P = .18); on multivariable analysis, a nonsignificant increase in ADHD was also found for assisted reproductive treatment children (hazard ratio 1.45, 95% confidence interval 0.81-2.61). Regarding the Child Symptom Inventory-4 criteria for ADHD among the children who had never been diagnosed, there was also a slightly higher but nonsignificant rate among the assisted reproductive treatments compared to spontaneously-conceived children on univariate (2.4% vs 1.8%; P = .50) and multivariable analysis (odds ratio 0.88, 95% confidence interval 0.27-2.86). Autism spectrum disorder diagnosis or Autism Spectrum Screening Questionnaire scores were not significantly different; however, 5 of the 6 children with autism spectrum disorder diagnoses were in the assisted reproductive treatment group. Neurodevelopmental measures were similar in both groups, although nonconclusive regarding ADHD and autism spectrum disorder risk. These findings contribute to the knowledge regarding long-term assisted reproductive treatment outcomes.

Concentrations of homocysteine in follicular fluid and embryo quality and oocyte maturity in infertile women: a prospective cohort

Homocysteine is one of the components of follicular fluid (FF), so that any disruptions in its concentration may affect oocyte development. The aim of this study was to determine the relationship between FF homocysteine concentration and embryo quality, oocyte maturity, and pregnancy rate. Oocytes and embryos of 44 infertile women were categorised into different groups based on their maturity and quality, respectively. FF homocysteine levels, oocyte maturity, embryo quality, and pregnancy status were measured. A significant association was observed between the levels of FF homocysteine ​and oocyte maturation rate (p = .00). The concentration of FF homocysteine was higher than 9.8 µm/L in women with oocyte maturation < 80%. Most of the good quality embryos belonged to homocysteine levels < 9.8 µm/L. Decreased FF homocysteine concentrations can significantly improve the oocyte maturation rate and embryo quality. Aging may be an indirect factor contributing to decreased embryo quality and oocyte maturation through increasing FF homocysteine levels. IMPACT STATEMENT What is already known on this subject? It has been demonstrated that homocysteine is one of the components of follicular fluid (FF), but no information is available about the link between its concentration in FF and oocyte development. What do the results of this study add? The data indicated that decreased FF homocysteine concentrations at a younger age may remarkably improve the oocyte maturity and embryo quality of infertile patients undergoing assisted reproductive treatment (ART). What are the implications of these findings for clinical practice and/or further research? Based on the findings and considering the ease of measuring serum homocysteine and its direct correlation with FF homocysteine, homocysteine level measurement is recommended in patients who are candidates for infertility treatment in order to estimate oocyte maturation rate, embryo quality, and ART outcomes. Future studies are suggested to investigate patients with PCOS, endometriosis, and male factor infertility.