Infertility Treatment Outcomes Research Articles

Evaluation of ovarian reserve and the assisted reproductive technology (ART) cycles’ outcome as well as the relapse rate within one year after ART in women with multiple sclerosis: a case-control study

ObjectiveTo compare the ovarian reserve and the results of infertility treatment, as well as to investigate the relapse rate in the first year after the assisted reproductive technology (ART) cycle in patients with multiple sclerosis (MS) referred to Royan Institute.Materials and methodsThis retrospective study was carried out to evaluate all women diagnosed with MS and referred to Royan Institute for assessment and treatment of possible infertility between 2011 and 2022. The control group consisted of randomly selected healthy women with tubal factor infertility who were referred for treatment during the same time period and matched in terms of age. A comparison was made between groups in terms of ovarian reserve and infertility treatment outcomes. Additionally, patients with MS who met the criteria were monitored via telephone to evaluate the symptoms, disability and relapse rate both pre- and post-ART.ResultsOver the course of a decade, the database documented a total of 60 cases diagnosed with MS. Upon examination of the records, it was found that in 27 patients only admission was done without any hormonal assessment or infertility treatment cycle and 5 patients proceeded with the intrauterine insemination cycle. Eventually, 28 women with MS underwent the ART cycle and all of them were treated with interferon beta, glatiramer acetate, or some oral disease modifying therapies. No statistically significant difference in terms of the basal levels of luteinizing hormone, follicle-stimulating hormone and anti-Müllerian hormone was found between the MS and control groups (P > 0.05). Two groups were comparable in terms of menstrual status. The study revealed that both groups exhibited similarities in terms of the controlled ovarian stimulation protocol and duration, the dosage of gonadotropin administered, as well as the ovarian response type, clinical pregnancy rate, and live birth rate (P > 0.05). After follow up, only 2 patients (9.5%) reported relapse of symptoms within one year after ART.ConclusionThe ovarian reserve and ovarian stimulation cycle and pregnancy outcomes following the ART cycle in MS patients were similar to the age-matched control group. The relapse rate of multiple sclerosis did not show a significant increase within a year following the ART cycle.

P-383 Development and validation of a visualized prediction model for early miscarriage risk in patients undergoing IVF/ICSI procedures: a real-world multi-center study

Abstract Study question What are the key predictors of early miscarriage in patients undergoing IVF/ICSI treatment? Summary answer This study identified risk factors for early miscarriage in IVF/ICSI patients, and developed a validated predictive nomogram, highlighting age-dependent factor variations. What is known already Early miscarriage, occurring in 15-20% of confirmed pregnancies, can lead to complications, psychological distress, and fertility impairment. It is especially prevalent during the first trimester, with up to 80% of all miscarriages happening during this phase. Women who conceive via Assisted Reproductive Technology (ART) face higher stress levels and increased risk of miscarriage. Although many contributing factors to early miscarriage have been identified, there is a scarcity of integrated predictive models for IVF/ICSI patients. This paper aims to develop a validated, user-friendly nomogram to predict first-trimester miscarriage risk in IVF/ICSI patients and help clinicians and patients make informed decisions. Study design, size, duration A retrospective analysis was conducted on 20,322 first cycles out of 31,307 for IVF/ICSI at a reproductive centre in Southern China, After excluding ineligible cycles, 6,724 first fresh cycles were included and randomly divided into a training dataset (n = 4,516) and an internal validation dataset (n = 2,208). An external validation dataset (n = 1,179) was obtained from a reproductive center in Northern China, further ensuring the robustness and generalizability of the findings. Participants/materials, setting, methods This retrospective study analysed 6,724 out of 31,307 IVF/ICSI treatments from 2011 to 2020 at a Southern China reproductive center and 1,179 cycles from a Northern China center (2013-2018) for validation. Early miscarriage was defined as a loss before 12 weeks’ gestation. Patients were divided into two age groups: ≥35 and <35 years. The study followed the TRIPOD statement and received Institutional Review Board approval. Main results and the role of chance The study found statistically significant differences across the training, internal validation, and external validation sets in terms of patient age, BMI, number of good quality embryos, antral follicle count (AFC), basal testosterone (T), luteinizing hormone (LH) levels, among other variables. The early miscarriage rates were 9.43%, 10.55%, and 13.50% across these sets. Elder women (age ≥35 years) had a higher duration of infertility and early miscarriage rate, but lower AFC and numbers of retrieved oocytes, 2PN, and MII oocytes compared to younger women (age <35 years). A nomogram prediction model was developed using variables such as female age, BMI, number of spontaneous abortions, number of induced abortions, and basal FSH, which were found to be independent prognostic factors for early miscarriage. The model’s performance was validated using AUC, calibration plots, and DCA, indicating acceptable performance and good agreement between prediction and observation. The model was more beneficial for predicting miscarriage risk than the treat-all or treat-none schemes. Subgroup analysis for elder and younger women showed different risk factors for miscarriage, notably female age, basal FSH for elder women, and female age, BMI, and the number of spontaneous abortions for younger women. The subgroup models also showed consistent results and good clinical relevance. Limitations, reasons for caution The retrospective design of our study may have introduced certain limitations and potential biases. To overcome these limitations, it is advisable that future research endeavors adopt a prospective clinical study design. Wider implications of the findings This study uses a diverse dataset and rigorous methods to create a user-friendly prediction model for early miscarriage in ART. By considering regional differences, it ensures the model’s broader applicability and accuracy, enabling personalized treatment strategies and improving infertility treatment outcomes. Trial registration number The study was a retrospective study, and it was approved by the Institutional Review Boards of Sun Yat-Sen Memorial Hospital (SYSEC-KY-KS-2021-121) and the First Affiliated Hospital of Xinjiang Medical University (K202106-17) and is reported in accordance with the TRIPOD statement

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

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

Lifestyle and fertility-specific quality of life affect reproductive outcomes in couples undergoing in vitro fertilization.

A Mediterranean dietary pattern, sleeping habits, physical activity, and lifestyle appear to affect reproductive health. There are few reports about whether fertility-specific quality of life (QOL) is linked to infertility treatment outcomes. The aim of this study is to investigate when lifestyle factors and fertility-specific QOL are comprehensively considered, which factors influence assisted reproductive technology (ART) outcomes. This prospective cohort includes 291 women undergoing a first ART treatment at multiple centers in Japan and was designed to evaluate the influence of diet, physical activity, sleeping pattern, computer use duration, and fertility-specific quality of life tool (FertiQoL) score on ART treatment outcomes using a questionnaire. The primary endpoint was the good-quality blastocyst rate per oocyte retrieval and the secondary endpoints were a positive pregnancy test and gestational sac (GS) detection. The good-quality blastocyst rate per oocyte retrieval tended to be negatively associated with frequent fish consumption. After all embryo transfer (ET) cycles, a positive pregnancy test tended to be positively associated with longer sleep and longer computer use (OR = 1.6, 95% CI = 0.9-2.7 and OR = 1.7, CI = 1.0-2.8, respectively) and negatively associated with a smoking partner (OR= 0.6, CI = 0.3-1.0). GS detection was positively and significantly associated with frequent olive oil intake and longer computer use (OR = 1.7, CI = 1.0-3.0 and OR = 1.7, CI = 1.0-3.0, respectively). After ET cycles with a single blastocyst, a positive pregnancy test was positively and significantly associated with longer computer use (OR = 2.0, CI = 1.1-3.7), while GS detection was significantly more likely in women with longer computer use (OR = 2.1, CI = 1.1-3.8) and tended to be more likely in women with a higher FertiQoL Total scaled treatment score (OR= 1.8, CI = 1.0-3.3). p < 0.05 was considered statistically significant and 0.05≤ p <0.01 as tendency. Olive oil may be an important factor in dietary habits. Fertility-specific QOL and smoking cessation guidance for partners are important for infertile couples.

The Effects of Thiamine Supplementation on General Health and Infertility Treatment Outcomes in Women with Polycystic Ovary Syndrome: A Triple-Blinded Randomized Placebo-Controlled Clinical Trial.

The aim of this study was to evaluate the effects of thiamine (vitamin B1) on general health and infertility treatment outcomes in women with polycystic ovary syndrome (PCOS). The study is a triple-blinded, randomized, placebo-controlled clinical trial performed on 64 infertile women with PCOS referred to Sarem Hospital in Tehran, Iran. The primary outcomes of the study were general health and infertility treatment outcomes. Eligible women were randomly assigned to the vitamin B1 group (n=32, vitamin B1 tablet at a dose of 300 mg/day for 4 weeks) or the placebo group (n=32, placebo tablet daily for 4 weeks). A general health questionnaire was completed before and after the intervention by both groups, and treatment success was evaluated at the end of the study. Data were analyzed using SPSS software ver.16 P<0.05 was considered statistically significant. The mean age of participants in the vitamin B1 (VB1) group was 30.4 ± 3.27 years and in the placebo (Pl) group was 29.1 ± 2.66 years with the mean duration of marriage 12.7 ± 3.01 and 13.2 ± 2.97 years respectively. Our results showed that there were significant differences between the two groups in overall score (P<0.001) and scores for all domains of the general health questionnaire including somatic symptoms (P<0.001), anxiety and insomnia (P<0.001), social dysfunction (P=0.028), and severe depression (P<0.001) after the intervention. Four weeks consumption of vitamin B1 also resulted in higher numbers of positive pregnancy tests (P=0.006), although the number of fetuses was not significantly different between the two groups after the intervention. The results of the current study support a possible favourable effect of vitamin B1 on improving general health, infertility treatment outcome, and retrieved follicle count without changing the number of fetuses in women with polycystic ovary syndrome (registration number: IRCT201510266917N3).

Does The Culture of Post-Thawed Cleavage-Stage Embryos to Blastocysts Improve Infertility Treatment Outcomes of Frozen-Thawed Embryo Transfer Cycles? A Randomised Clinical Trial.

There is a definite shift in assisted reproductive centres from cleavage-stage embryo transfer (ET) to blastocyst transfer that is attributed to improvements in laboratory environments and advances in the development of embryo culture media. The aim of the study was to investigate the reproductive outcomes of thawed cleavage-stage ET versus blastocysts derived from an extended culture of these embryos. This open-label, randomised, parallel group clinical trial study enrolled 182 women aged ≤37 years who underwent frozen-thawed ET from November 2015 to June 2020 at Royan Institute Research Centre, Tehran, Iran. The women were randomly assigned to either the thawed cleavage ET group (n=110) or the post-thaw extended culture blastocysts group (n=72). The primary outcome measure was the clinical pregnancy rate. Secondary outcome measures were implantation rate, live birth rate (LBR), and miscarriage rate. A P<0.05 indicated statistical significance. There were no significant differences between the two groups in terms of demographic characteristics. Both the mean numbers of embryos transferred and good quality embryos transferred were significantly lower in the postthaw extended culture blastocysts group compared to thawed cleavage-stage ET cycles. However, the post-thaw extended culture blastocysts group had higher clinical pregnancy (56.94 vs. 40.91%, P=0.034), implantation (34.43 vs. 19.84%, P=0.001) and live birth (49.3 vs. 33.63%, P=0.036) rates compared to the thawed cleavage-stage ET group. Miscarriage and multiple gestations rates were comparable between the groups. These results allow us to take a position in favour of post-thaw extended culture blastocysts; thus, it is important to improve the post-thawing extended culture technique (registration number: NCT02681029).

Ectopic expression of the mitochondrial protein COXFA4L3 in human sperm acrosome and its potential application in the selection of male infertility treatments.

Spermatogenesis requires a large amount of energy, which is primarily produced by the mitochondrial electron transfer chain. Mitochondrial dysfunction affects male infertility, suggesting a relationship between the electron transfer chain and male infertility. COXFA4L3 (C15ORF48) is an emerging subunit protein of cytochrome oxidase specifically expressed in germ cells during spermatogenesis, and it may be involved in male infertility. Therefore, to investigate whether COXFA4L3 could be a marker of mitochondrial dysfunction in the sperm, this study examined the protein expression and localization profile of COXFA4L3 in the sperm of male patients with infertility. Twenty-seven semen samples from a male infertility clinic at the Reproductive Center of Yokohama City University Medical Center were used to analyze sperm quality parameters and the expression and localization of energy production-related proteins. These data were compared with the outcomes of infertility treatment. The expression levels of COXFA4L3 varied significantly between samples. Furthermore, COXFA4L3 was ectopically localized to the acrosome. Ectopic expression of COXFA4L3 and PNA-stained acrosomes may be useful parameters for fertility treatment selection. Assessing the acrosomal localization of COXFA4L3 will expedite pregnancy treatment planning.

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

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

ASSESSING THE EFFICACY OF LONG-PROTOCOL OVULATION STIMULATION USING GONADOTROPIN-RELEASING HORMONE AGONIST IN WOMEN EXPERIENCING INFERTILITY AND COMORBIDITY OF LEIOMYOMA AND CHRONIC ENDOMETRITIS

Introduction. Nowadays infertility is one of the global medical and social issues worldwide. Assisted reproductive technologies, including in vitro fertilization, is one of the main techniques for restoring fertility. Among the main stages of IVF are controlled ovarian stimulation (COS), the optimal method of which is chosen depending on a numerous factor, such as the patient's age, the ovarian reserve, and the presence of concomitant gynecological or extragenital pathology. The prevalence of various combinations of gynecological pathologies, for example, the comorbidity of uterine leiomyoma and chronic endometritis, can affect the results of IVF in different ways, so scientists around the world are increasingly studying the management of such patients. The aim of the study is to compare controlled ovarian stimulation long-protocol parameters and its effectiveness in the therapy of infertile patients with the comorbidity of uterine leiomyoma and chronic endometritis. Methods and participants. We performed retrospective comparative analysis of anamnestic data of 130 women with infertility who underwent infertility treatment with assisted reproductive technologies. The patients were divided into three groups. In all groups, stimulation of superovulation was carried out following a long protocol with a GnRH agonist; p&lt;0.05 was considered statistically significant during the statistical data processing. Results. The study has revealed that higher starting dose of gonadotropins, as well as higher total gonadotropin consumptions are required for the patients of the second study group with uterine leiomyoma and chronic endometritis, compared to the first study group and the control group. The number of retrieved oocytes, including mature ones, were the lowest as well as the number of immature, deeply immature and degenerative oocytes were the highest in the second study group. The lowest rate of normal fertilization (2pn) and, as a result, a lower blastocyst yield is recorded in the same group. The highest frequency of aborted pregnancies among achieved clinical pregnancies is observed in the group of infertile women with uterine leiomyoma and chronic endometritis. Conclusions. The presence of the uterine cavity pathology combined with persistent chronic inflammation of the uterine mucosa, as well as the absence of proper preparation for IVF-ET cycles are the main reasons for the negative infertility treatment outcomes in such patients. This justifies the need for appropriate optimal preparation and elimination of the identified negative factors before or during the infertility treatment.

Self-reported occupational exposure and its association with sperm DNA fragmentation in infertile men

Background/Aim: Sperm quality has experienced a decline in recent years, with this issue being particularly pronounced in industrialized nations, suggesting a potential link to occupational exposures. Evaluating sperm DNA fragmentation can yield valuable insights into male fertility, although its association with occupational exposures remains less well-established. Our study aimed to investigate the relationship between self-reported occupational exposures and sperm DNA fragmentation in infertile men. Methods: This retrospective cohort study involved 391 infertile men who sought fertility treatment at a university clinic between 2017 and 2020. A brief questionnaire was administered to collect data on patients’ demographic characteristics, medical history, occupation, and exposure types. In this comparative study, patients were categorized into two groups based on their occupational exposures (the unexposed and exposed groups). The exposed group was further sub-grouped according to their specific exposure types, which included cement, solvents, metals, pesticides, mechanical vibration, and heat. The primary outcome in this study was assessed using the terminal deoxynucleotidyl transferase-mediated nick end-labeling test (TUNEL), with results expressed as the sperm DNA fragmentation index (DFI). Results: Patients in the exposed group exhibited a significantly higher sperm DFI compared to those in the unexposed group (14 [17] vs. 8 [9], P&lt;0.001). After accounting for potential confounding factors, our results demonstrated that several occupational exposure factors significantly increased the risk of elevated sperm DFI (&gt;15%) levels, including solvents (odds ratio (OR)=8.2, 95% confidence interval (CI)=3.6–18.5, P&lt;0.001), metals (OR=2.2, 95% CI=1.0–4.7, P=0.048), pesticides (OR=14.6, 95% CI=1.6–130.7, P=0.016), mechanical vibration (OR=2.6, 95% CI=1.5–4.6, P&lt;0.001), and heat (OR=6.4, 95% CI=1.7–23.5, P=0.005). Conclusion: The findings of our study corroborate earlier research suggesting that occupational exposures may have adverse effects on sperm DNA fragmentation in men. The identification and management of such exposures as part of routine clinical practice could offer a complementary approach to enhancing infertility treatment outcomes.

The associations of preconception urinary phthalate metabolite concentrations with the serum metabolome and outcomes of infertility treatment

The associations of preconception urinary phthalate metabolite concentrations with the serum metabolome and outcomes of infertility treatment

Women’s Adherence to Healthy Dietary Patterns and Outcomes of Infertility Treatment

Increasing evidence suggests that specific foods and nutrients may improve infertility treatment outcomes in women. However, less is known about the role of dietary patterns. To investigate whether women's adherence to a priori-defined dietary patterns promoted for the prevention of chronic conditions is associated with outcomes of infertility treatment. This prospective cohort study was conducted at a fertility center at an academic medical center in Boston, Massachusetts. Women undergoing infertility treatment cycles, including intrauterine insemination cycles and in vitro fertilization with or without intracytoplasmic sperm injection were included. Data were collected from January 2007 to October 2019, and data were analyzed from February to December 2022. Women's pretreatment diet was assessed with a validated food frequency questionnaire from which 8 a priori-defined scores were calculated (higher score indicates greater adherence): (1) Trichopoulou Mediterranean diet, (2) alternate Mediterranean diet, (3) Panagiotakos Mediterranean diet, (4) Healthy Eating Index, (5) Alternate Healthy Eating Index, (6) American Heart Association (AHA) index, (7) Dietary Approaches to Stop Hypertension index, and (8) plant-based diet. The adjusted probability of clinically relevant outcomes (live birth as a primary outcome and clinical pregnancy and pregnancy loss as secondary outcomes) was evaluated across quartiles of adherence to each dietary pattern using multivariable generalized linear mixed models to account for repeated cycles. This analysis included 612 women with a median (IQR) age of 35.0 (32.0-38.0) years. There was no association between women's adherence to the 8 a priori dietary patterns and probability of clinical pregnancy or live birth following in vitro fertilization or intrauterine insemination. However, an inverse association was found between adherence to AHA dietary pattern and risks of total and clinical pregnancy loss. Among women who became pregnant during the course of infertility treatment, the adjusted probabilities of pregnancy loss in the lowest and highest quartile of the AHA dietary pattern were 0.41 (95% CI, 0.33-0.50) and 0.28 (95% CI, 0.21-0.36), respectively (P for trend = .02). The corresponding adjusted probabilities of clinical pregnancy loss were 0.30 (95% CI, 0.22-0.39) and 0.15 (95% CI, 0.10-0.23) (P for trend = .007). A similar pattern was observed for all other dietary patterns, with the exception of the plant-based diet pattern. Findings of this cohort study suggest that preconception adherence to the AHA diet may be associated with a lower likelihood of pregnancy loss during the course of infertility treatment.

Baseline Dietary Patterns and Infertility Treatment Outcomes—Setting the Right Foundation

Baseline Dietary Patterns and Infertility Treatment Outcomes—Setting the Right Foundation

Analysing medical predictors for the outcome of infertility treatment: a 5-year follow-up survey

PurposeFor many couples, bearing children is a common life goal; however it cannot always be fulfilled. Undergoing infertility treatment does not always guarantee pregnancies and live births. Couples experience miscarriages and even discontinue infertility treatment. Significant medical predictors for the outcome of infertility treatment have yet to be fully identified.MethodsTo further our understanding, a cross-sectional 5-year follow-up survey was undertaken, in which 95 women and 82 men that have been treated at the Women’s Hospital of Heidelberg University participated. Binary logistic regressions, parametric and non-parametric methods were used for our sample to determine the relevance of biological (infertility diagnoses, maternal and paternal age) and lifestyle factors (smoking, drinking, over- and underweight) on the outcome of infertility treatment (clinical pregnancy, live birth, miscarriage, dropout rate). In addition, chi-square tests were used to examine differences in the outcome depending on the number of risk factors being present.ResultsIn the binary logistic regression models for clinical pregnancies, live births and drop outs were statistically significant only for the maternal age, whereas the maternal and paternal BMI, smoking, infertility diagnoses and infections showed no significant predicting effect on any of the outcome variables. A correlation between the number of risk factors and the outcome of infertility treatment could not be excluded.ConclusionThe results confirm that maternal age has an effect on infertility treatment, whereas the relevance of other possible medical predictors remains unclear. Further large-scale studies should be considered to increase our knowledge on their predictive power.

O-097 Predicting live birth rate using combined Day3-spent embryo culture medium metabolomics and cumulus cell gene expression based algorithm to optimize embryo selection in unexplained infertility

Abstract Study question Can combination of metabolomics of spent embryo culture medium (sECM) and cumulus cell (CC) genes judge live birth rate in unexplained infertility (UI)? Summary answer A combination of day3 metabolic profiling of sECM with CC gene expression yields an algorithm to predict live birth rate in UI. What is known already Optimizing embryo selection is rate-limiting for pregnancy success. The metabolomic profile of sECM can aid in advanced prediction of embryonic developmental potential. Recent transcriptomics studies proposed prokinectin 2 (PROK2), and pregnancy up-regulated nonubiquitous CaM kinase (PNCK) as two novel gene/s responsible for perifollicular vascularization and embryonic development respectively; two important events regulating bidirectional CC-oocyte signalling and implantation ability. Given that UI is contributory to impaired oocyte quality, we delineated if combined metabolic signature of CC gene expression encompassing metabolic, developmental competence, and extracellular matrix facet/s and sECM could address live birth rate in women with UI following single embryo transfer. Study design, size, duration A prospective cohort study was conducted at Institute of Reproductive Medicine between January 2022 and October 2022. 48 women (age: 30-39 years) diagnosed with UI undergoing oocyte-retrieval offered consented participation and were sub-stratified according to pregnancy outcome. Cleavage-stage embryos from intra cytoplasmic sperm injection (ICSI) cycles were scored according to combination of gene expression pattern of CC-samples and integral value of metabolite obtained from nuclear magnetic resonance (NMR) spectroscopy of sECM (range 0-3, 4-6, 7-9). Participants/materials, setting, methods Expression profiles of metabolic (LDHA, PFKP, PKM2), extracellular matrix (HAS2, PTX3, TNFAIP6, VCAN), and developmental competence (PNCK, PROK2) related genes were evaluated by real time-quantitative polymerase-chain-reaction (qRT-PCR) from retrieved CC. Day-3 sECM (30 μL) was collected for NMR from 43 single transferred embryos. Univariate and multivariate analysis was performed after NMR data acquisition. Live birth rate was evaluated by area-under-the-curve (AUC) values using combined score panel. Main results and the role of chance The groups were similar for patient age, BMI, AMH, infertility diagnosis, and stimulation protocol. A total of 43 cycles were included in the analysis [embryo transfer cancelled (n = 2), insufficient cumulus mass (n = 3)]. Clinical pregnancy was confirmed in 16 patients (37.21%). Mean mRNA levels for all genes were similar in CC associated with oocyte that fertilized normally (2PN) compared with those that either failed to fertilize or were abnormal (i.e. 1PN, 3PN). Similar results were observed in terms of speed of embryonic cleavage (≥7 cell on Day 3 vs. ≤6 cell on Day 3). Expression of VCAN, (OR: 1.102, 95% CI: 1.010-1.202, p &amp;lt; 0.02), PNCK (OR: 0.931, 95% CI: 0.916-0.947, p &amp;lt; 0.001) and PROK2 (OR: 1.273, 95% CI: 1.011-1.231, p &amp;lt; 0.001) was significantly higher (p &amp;lt; 0.01) in CC that achieved live birth compared with those that failed to result a successful pregnancy. Multivariate and univariate analysis revealed distinct metabolomic signatures between pregnant and non- pregnant group/s. Lactate, pyruvate and proline were the most significant (p &amp;lt; 0.01) altered metabolite in sECM of non-pregnant group when compared to their pregnant counterpart. The combination demonstrated a “good” (VCAN, pyruvate: AUC: 0.87), “fair” (PROK2, proline: AUC: 0.79) and “modest” (PNCK, glucose: AUC: 0.71) in terms of live-birth rate. Limitations, reasons for caution The study population is heterogeneous in terms of duration of infertility and previous infertility treatment outcome, limited by small sample size and subjective nature of embryo scoring. The presumable involvement of unknown factors in developmental competence of UI and impact of frozen cycle/s should also be addressed. Wider implications of the findings The study provides reliable accuracy measures to support relationship between live birth rate and combined score panel in patients with UI. It is envisioned integration of CC gene expression/s and metabolomics of sECM if combined with patient characteristics may tailor therapy by artificial intelligence to model the outcome in UI. Trial registration number Not applicable

Pregnancy Outcomes Associated with Ovarian Hyperstimulation Syndrome: A Retrospective Cohort Study of Infertile Women.

To assess the relationship between ovarian hyperstimulation syndrome (OHSS) and adverse outcomes using population-based data in the United States. The hypothesis is that patients with OHSS were more likely to deliver preterm and more likely to have hypertensive disorders. This retrospective cohort study identified 94 patients with OHSS and 183 matched referents in eight counties in Minnesota. Data were collected regarding pregnancy history, infertility treatment, and pregnancy outcomes. Using the Rochester Epidemiology Project, study subjects were identified from female patients, aged 18 to 49 years, who were diagnosed with infertility from January 2, 1995 to December 1, 2017, and had a pregnancy greater than 20 weeks' gestation. The primary outcome was preterm delivery or hypertensive disorder of pregnancy incidence in the OHSS group when compared with control patients. Chi-squared test, t test, and multivariate logistic models were used where appropriate. Patients with OHSS were more likely to deliver preterm (odds ratio, 2.14; 95% confidence interval, 1.26-3.65; P < 0.01), and their neonates were more likely to be small for gestational age (odds ratio, 4.78; 95% confidence interval, 1.61-14.19; P < 0.01). No significant differences between the groups were observed in any other outcome. Patients with OHSS are more likely to deliver preterm if they undergo fresh transfer compared with a freeze all and subsequent frozen transfer (odds ratio, 3.03, 95% confidence interval, 1.20-7.66, P = 0.02). OHSS may lead to preterm birth and small-for-gestational-age neonates, which changes patient counseling and leads to arranging specialized obstetrical care for these patients with OHSS.

Association of chorioamnionitis with infertility treatment and subsequent neonatal outcomes in the US: a population-based cohort study

BackgroundChorioamnionitis (CAM) is a common risk factor for preterm births, resulting in several adverse outcomes. The association between infertility treatment and CAM is unclear. Therefore, this study examined the association between infertility treatment and CAM and described subsequent neonatal outcomes.MethodsThis population-based cohort study used data from the National Vital Statistics System Database. We included women who had a singleton live birth from January 1, 2016 to December 31, 2018. Women-infant pairs were stratified by infertility treatment, and the main outcome was a reported diagnosis of CAM in a checkbox format: clinical CAM or maternal temperature of > 38 °C. Multivariate logistic regression was used to examine the association between infertility treatment and CAM and the effect of infertility treatment on neonatal outcomes in women diagnosed with CAM.ResultsThe final sample comprised 10,900,495 woman-infant pairs, and 1.4% received infertility treatment. Compared with the natural conception group, women receiving infertility treatment had a significantly higher risk of CAM (adjusted odds ratio [aOR] 1.772 [95% confidence interval {CI}, 1.718–1.827]). Furthermore, newborns exposed to CAM had a higher risk of very low birth weight (VLBW) (aOR, 2.083 [95% CI, 1.664–2.606], P < .001), preterm birth (aOR, 1.497 [95% CI, 1.324–1.693]; P < .001), neonatal intensive care unit admission (aOR, 1.234 [95% CI, 1.156–1.317]; P < .001), and other adverse neonatal outcomes in the infertility treatment group compared with ones conceived naturally.ConclusionsThis study found that women who received infertility treatment had a higher risk of CAM. And CAM deteriorated neonatal outcomes in the infertility treatment group.

The influence of reproductively significant autoantibodies determined in the follicular fluid on the quality of the obtained oocytes and embryos, as well as on the implantation rate in assisted reproductive technology cycles

BACKGROUND: According to reports, the efficiency of in vitro fertilization and intra cytoplasmic sperm injection protocols is decreased in patients positive for various autoantibodies, as opposed to autoantibody negative patients. However, there are contradictory data indicating no autoantibody effect on the outcome of infertility treatment using assisted reproductive technology.&#x0D; AIM: The aim of this study was to evaluate the embryological outcome and clinical efficiency of infertility treatment in in vitro fertilization and intra cytoplasmic sperm injection protocols in women in the presence of reproductively significant autoantibodies.&#x0D; MATERIALS AND METHODS: This prospective study enrolled 90 infertile patients undergoing assisted reproductive technology treatment. The follicular fluid obtained on the day of oocyte retrieval was evaluated for a wide autoantibody panel using commercial ELISA kits. The main group (n = 52) included women with autoantibody levels determined in the follicular fluid of more than three standard deviations from the mean values determined among all patients. The comparison group consisted of 38 women with autoantibody levels of less than three standard deviations from all subjects. The intergroup comparative analysis included clinical and anamnestic data, hormonal parameters, ovarian reserve, embryological data, and in vitro fertilization and intra cytoplasmic sperm injection efficiency.&#x0D; RESULTS: Reliably lower ovarian reserve parameters (anti-Mullerian hormone levels 1.9 (1.4; 4.0) vs. 3.3 (2.2; 6.5) ng/ml; p = 0.005; number of antral follicles 8.5 (6.0; 12.0) vs. 11.0 (9.0; 17.0); p = 0.003) have been noted in the main group relatively to the comparison group. The autoantibodies to thyroid peroxidase and cardiolipin content in the follicular fluid has been shown to be negatively associated with the number of two-pronuclear zygotes, the presence of autoantibodies to aromatase correlating negatively with the fertilization rate. Furthermore, the follicular fluid levels of autoantibodies to thyroid peroxidase (105 IU/ml) and cardiolipin (5.1 IU/ml) are reliably associated with a higher frequency of a suboptimal response to previous controlled ovarian stimulation, a lower incidence of high quality embryos on days 3 and 4 of in vitro cultivation, a decreased number of top-quality blastocysts, and the clinical efficiency of in vitro fertilization and intra cytoplasmic sperm injection programs.&#x0D; CONCLUSIONS: The presence of reproductively significant autoantibodies is an independent risk factor for reducing the total efficiency of assisted reproductive technology treatment.

Impact of duration of Infertility on the Physiological Viability of Sperms Preparing for Intrauterine Insemination among Yemeni Infertile Males

Background :The duration of infertility should be considered as a factor that may affect the outcome of assisted reproductive techniques (ART).Aim :The aim of this descriptive study was to examine the outcome of infertility treatment in relation to duration of infertility. Methods: Sixty nine couples from Allow in vitro fertilization center (IVF) were involved in this work. Intrauterine insemination (IUI) had been done for all couples using the same ART. Results: The mean age of men was 29.37±0.16 years and the duration of infertility was 4.38±0.25 years with range of 1-12 years. Higher pregnancy and life-birth rates were demonstrated in males suffering from infertility for less than 4 years as compared to those who had infertility for more than 10 years (P&lt;0.003, r = -0.869). Moreover, abortion rate was higher in men who had infertility for more than 10 years as compared to those who have infertility for less than 4 years (P&lt;0.0014).. The linear life-birth rate, in both IVF centers, shows decrease by increase in the duration of infertility. Conclusion: The researchers conclude that by increase in the duration of infertility the outcome of assisted reproductive techniques –IUI will be decreased markedly. In addition to the duration of infertility, the present work recommended to consider the different techniques of sperm preparation in relation to the ART outcome.

Access to infertility care and ART treatment in India: A clinician's perspective

Infertility is a worldwide problem that is increasing with time. The cause of infertility can be due to either male or female factors or both. The food, environmental, occupational and psychological factors do contribute to infertility. The infertility and the present scenario of assisted reproductive technology (ART) in India with regard to the clinics, clinicians and regulatory mechanisms in vogue are discussed. The potential of India as a reproductive tourist destination and surrogacy issues is included. The social, economic, and family problems arising as a consequence of infertility are discussed. The status of ART in India is getting improved and the gap between the West and India is expected to be minimized with the influence of regulatory mechanisms introduced through ART Act in India. The salient features that have a bearing on the infertility treatment outcomes, which are being neglected, or recent findings of research are included with special reference to possible future developments in the field of ART.