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Background: Treatment of endometrioma before in vitro fertilization (IVF) is challenging as it may affect ovarian response to induction. Objective: A systematic review to search for the available optimal management of ovarian endometrioma before ovulation induction in IVF. Search strategy: Screening of the MEDLINE, Web of Science, EMBASE, Cochrane database, and the clinical trial registration sites, covering the period from their inception up to June 2023 was done by two reviewers independently using the keywords ovarian endometrioma, ovarian endometriosis, endometrioma/surgery, endometrioma/hormonal treatment, randomized controlled trial(s), case-controlled studies, and cohort studies. Selection criteria: All types of studies were included. Participants included were women with unilateral or bilateral ovarian endometriomas candidate for IVF/ICSI. We included 18 studies in the review. Three studies were randomized controlled parallel studies, six were prospective cohort, and nine were retrospective cohort studies. Data collection and analysis: Data from all included studies were extracted by two authors (A. M., A. O.) independently. Data extracted included sample size, population characteristics including age, BMI, duration of infertility, ovarian reserve markers, cyst size, and bilaterality and induction protocol used. Main results: We found 18 studies. Women with untreated endometrioma had significantly higher numbers of MII oocytes (the mean difference (MD) effect estimate was − 0.53 with [− 1.04, − 0.01] 95% CI and 0.04 P-value), higher number of obtained embryos (MD effect estimate was − 0.25 with [− 0.38, − 0.11] 95%CI and < 0.001 P-value), and required lower doses of gonadotropins for induction (MD effect estimate was 361.14 with [168.13, 5554.15] 95% CI and < 0.001 P-value) compared to those who had undergone surgical management of endometrioma. However, live birth (OR effect estimate was 0.79 with [0.54, 1.18] 95% CI and 0.25 P-value), clinical pregnancy (OR effect estimate was 0.95 with [0.72, 1.26] 95% CI and 0.73 P-value), miscarriage (OR effect estimate was 0.74 with [0.33, 1.63] 95% CI and 0.45 P-value), cancellation rates (OR effect estimate was 1.62 with [0.57, 4.66] 95% CI and 0.37 P-value), and the duration of stimulation (MD effect estimate was 0.19 with [− 0.42, − 0.81] 95% CI and 0.54 P-value) did not show any significant difference between the two groups of women. Hormonal treatment of endometrioma was associated with higher ongoing pregnancy rate (OR effect estimate was 3.39 with [1.83, 6.26] 95% CI and < 0.001 P-value), higher clinical pregnancy rate (OR effect estimate was 3.36 with [2.01, 5.63] 95% CI and < 0.001 P-value), and higher numbers of MII oocytes (MD effect estimate was 2.04 with [0.72, 3.36] 95% CI and 0.003 P-value) when compared to women who did not receive such therapy. These effects were evident in treatment with GnRH agonists, OCPs (oral contraceptive pills), and dienogest, while the miscarriage and cycle cancellation rates did not show these differences. Conclusions: The optimal approach for treating endometrioma prior to IVF is not clear yet due to lack of well-designed randomized controlled trials. Registration number: CRD42020151736. [ABSTRACT FROM AUTHOR]

Abstract Purpose The introduction of the time-lapse monitoring system (TMS) and the development of predictive algorithms could contribute to the optimal embryos selection for transfer. Therefore, the present study aims at investigating the efficiency of KIDScore and iDAScore systems for blastocyst stage embryos in predicting live birth events. Methods The present retrospective study was conducted in a private IVF Unit setting throughout a 10-month period from October 2021 to July 2022, and included the analysis of 429 embryos deriving from 91 IVF/ICSI cycles conducted due to infertility of various etiologies. Embryos incubated at the Embryoscope+ timelapse incubator were analyzed through the established scoring systems: KIDScore and iDAScore®. The main outcome measure was the comparison of the two scoring systems in terms of live birth prediction. Embryos with the higher scores at day 5 (KID5 score/iDA5 score) were transferred or cryopreserved for later use. Results Embryos with high KID5 and iDA5 scores positively correlated with the probability of successful live birth, with KID5 score yielding a higher efficiency in predicting a successful reproductive outcome compared to a proportionally high iDA5 score. KID5 demonstrated conservative performance in successfully predicting live birth compared to iDA5 score, indicating that an efficient prediction can be either provided by a relatively lower KID5 score or a relatively higher iDA5 score. Conclusion The developed artificial intelligence tools should be implemented in clinical practice in conjunction with the conventional morphological assessment for the conduction of optimized embryo transfer in terms of a successful live birth.

Objective: To investigate the effects of b-cell dysfunction on IVF outcomes in women with PCOS. Methods: This retrospective cohort study includes 1,212 women with PCOS undergoing their first IVF cycle between September 2010 and December 2019. Beta-cell dysfunction was measured by homeostasis model assessment of b-cell function (HOMA-b) index. Results: In quartiles of HOMA-b, the incidence of miscarriage dramatically increased from 10.2% (Q1) to 31.1% (Q4) (P for trend <0.001). Likewise, the incidence of miscarriage in quartiles of HOMA-b also showed a similar trend (P for trend <0.001). After adjusting for confounding factors, logistic regression analyses showed that high HOMA-IR values were independently associated with a high risk of miscarriage, with the odds ratios (OR) and 95% confidence intervals for quartiles 2-4 versus quartile 1 were 1.30 (0.69-2.46), 1.82 (0.97-3.43), and 3.57 (1.86-6.85), respectively (P for trend <0.001). When analyzed jointly, women in the highest HOMA-IR and highest HOMA-b group exhibited the highest risk for miscarriage compared with all other groups. Furthermore, higher HOMA-IR values were associated with higher risks of miscarriage among PCOS women regardless of HOMA-b values. Conclusions: b-cell dysfunction is independently associated with increased miscarriage rate and decreased live birth rate in women with PCOS. It also plays a synergistic role with IR in terms of the reproductive outcomes, while the influence of IR overweighs that of b-cell dysfunction. [ABSTRACT FROM AUTHOR]

• There have been concerns about the adverse effects of Covid-19 on IVF outcome with studies showing variable results. • The pooled analysis of studies comparing IVF outcome post Covid-19 recovery with controls failed to show any significant effect on the IVF outcome. • The results need to be interpreted with caution as the review is based only on observational studies each involving small number of participants. Study Question : What is the effect of SARS Cov-2 on IVF outcome? Summary answer : Mild or asymptomatic Covid-19 infection does not appear to affect clinical or ongoing pregnancy rate after IVF. What is already known : Covid-19 has been shown to affect female and male fertility and reproductive function. Studies have shown variable results regarding impact of Covid-19 on IVF outcome with few reporting impaired ovarian reserve, oocyte and embryo quality, semen parameters, clinical pregnancy rate (CPR) and live birth rate (LBR) while others reported no effect on IVF outcome. An electronic database search of PubMed, EMBASE, SCOPUS, WHO Covid-19 database, Clinical trials.gov and Cochrane Central was performed for articles published in English language between 1st January 2020 and 15th October 2022 by two independent reviewers using predefined eligibility criteria We have included observational studies both prospective and retrospective, cohort studies, and case control studies and excluded narrative reviews, case studies, cost-effectiveness studies or diagnostic studies. Risk of bias was assessed using NOS and quality of evidence was graded by GRADE pro. Studies comparing women undergoing IVF and comparing Covid-19 affected with those unaffected by Covid-19 were included. Also, studies comparing immune group (infected or vaccinated) in the study group and unaffected as controls (historical controls, IVF cycles done prior to Covid-19 outbreak but matched with study group) were included. Those with no comparison group or published in language other than English language or duplicate studies were excluded. We identified 5046 records and after full text screening of 82 studies, 12 studies were selected for final review. For the clinical pregnancy rate, there was no difference in the CPR in covid recovered or control patients (OR 0.90, 95 % CI = 0.67 to1.21; I2 = 29 %). Similarly, there was no significant effect on implantation rate (RR 0.92, 95 % CI = 0.68 to1.23; I2 = 31 %) and ongoing pregnancy rate (RR 0.96, 95 % CI = 0.79 to 1.15;I2 = 21 %). The mean number of the oocyte retrieved per patient was not significantly different in both the groups (mean difference 0.52, 95 % CI = -1.45 to 2.49; I2 = 75 %). The certainty of the evidence was low. Limitations: The meta -analysis is based on observational studies each involving small number of participants. Few studies reported outcomes as per patient while others reported as per cycle, for uniformity we have reported outcomes as per cycle. Sample size in most of studies was small. Wider Implications of findings: This systematic review has not shown any significant effect on the outcome of IVF cycles in patients post Covid-19 recovery compared to controls. But given the sample size, the findings should be considered with caution. Registration: The review protocol has been registered on PROSPERO (registration number CRD42022314515) [ABSTRACT FROM AUTHOR]

Abstract Backgroud Several studies showed that human papillomavirus (HPV) affects male fertility, but its impact on female fertility and in vitro fertilization (IVF) outcome is not yet clear. Methods Objective of this observational, prospective, cohort study was to evaluate the prevalence of HPV infection in women candidate to IVF, and the effects of HPV infection on the kinetic of embryonic development and on IVF outcome. A total number of 457 women candidate to IVF were submitted to HR-HPV test; among them, 326 underwent their first IVF cycle and were included in the analysis on IVF results. Results 8.9% of women candidate to IVF were HPV-positive, HPV16 being the most prevalent genotype. Among the infertility causes, endometriosis was significantly more frequent in HPV-positive than in negative women (31.6% vs. 10.1%; p

Abstract Background Intracytoplasmic sperm injection (ICSI) has become a common method of fertilization in assisted reproduction worldwide. However, there are still gaps in knowledge of the ideal IVF-ICSI workflow including the optimal duration of time between induction of final oocyte maturation, oocyte denudation and ICSI. The aim of this study was to examine outcomes following different workflow protocols in IVF-ICSI procedures in blastocysts that have undergone undisturbed incubation and preimplantation genetic testing for aneuploidy (PGT-A) prior to transfer. Methods Retrospective secondary analysis of 113 patients (179 IVF cycles, 713 embryos), all of whom have gone through IVF-ICSI and PGT-A using undisturbed culture. Predictive test variables were the length of time from: trigger to OPU, OPU to denudation, and denudation to ICSI. Outcome metrics assessed were: maturation, fertilization, blastulation and euploid rates. Generalized Estimated Equations Linear Model was used to examine the relationship between key elements of a given cycle and continuous outcomes and LOESS curves were used to determine the effect over time. Results In a paired multi-regression analysis, where each patient served as its own control, delaying OPU in patients with unexplained infertility improved both maturation and blastulation rates (b = 29.7, p

Abstract Background The cryopreservation of sperm or embryos has been an important strategy in the treatment of infertility. Recently studies have revealed the outcomes after IVF (in vitro fertilization) treatment for single-factor exposure either to frozen sperm or embryos. Methods This retrospective study was to uncover the exposure to both frozen sperm and embryo effects using IVF/H (in vitro fertilization using husbands’ fresh sperm) or IVF/D (in vitro fertilization using donors’ frozen sperm) treatment. Results The results showed the clinical pregnancy rate (CPR), live birth rate (LBR) and low birth weight rate (LBW) increased to 63.2% (or 68.1%), 61.1% (or 66.4%) and 15.8% (or 16.2%) after using frozen embryo transfer within Group IVF/H (or Group IVF/D). After using frozen sperm, the high-quality embryo rate (HER) increased to 52% and baby with birth defect rate (BDR) reduced to 0% in subgroup D/ET comparing to subgroup H/ET. While the fertilization rate (FER), cleavage rate (CLR), HER and multiple pregnancy rate (MUR) reduced to 75%, 71%, 45% and 9.2% in subgroup D/FET comparing to subgroup H/FET. Finally, our study found accumulative frozen gamete effects, including both sperm and embryos, led to the significantly increasing in the HER (p

Introduction: Dysregulation of the stress-regulatory hormone cortisol is associated with anxiety, but its potential impact on infertile women and in vitro fertilization (IVF) treatment remains unclear. This prospective cross-sectional study aimed at evaluating the dysregulation of cortisol and its correlation to anxiety in infertile women. The influence of stress on IVF outcomes was also investigated. Methods: A point-of-care test was used for the measurement of morning serum cortisol in 110 infertile women and 112 age-matching healthy individuals. A Self-Rating Anxiety Scale (SAS) was used for the anxiety assessment of infertile women, and 109 of them underwent IVF treatment starting with the GnRHantagonist protocol. If clinical pregnancy was not achieved, more IVF cycles were conducted with adjusted protocols until the patients got pregnant or gave up. Results: Higher morning serum cortisol level was identified for infertile patients, especially for the elder. Women with no anxiety showed significant differences in cortisol levels, monthly income, and BMI compared with those with severe anxiety. A strong correlation was found between the morning cortisol level and the SAS score. When the cutoff value is 22.25 &#μg/dL, cortisol concentration could predict the onset of anxiety with high accuracy (95.45%) among infertile women. After IVF treatments, women with high SAS scores (>50) or cortisol levels (>22.25 &#μg/dL) demonstrated a lower rate of pregnancy (8.0%-10.3%) and more IVF cycles, although the impact of anxiety was not affirmative. Conclusion: Hypersecretion of cortisol related to anxiety was prevalent among infertile women, but the influence of anxiety on multi-cycle IVF treatment was not affirmative due to the complicated treatment procedures. This study suggested that the assessment of psychological disorders and stress hormone dysregulation should not be overlooked. An anxiety questionnaire and rapid cortisol test might be included in the treatment protocol to provide better medical care. [ABSTRACT FROM AUTHOR]

Research question: To investigate differences in reproductive outcomes among IVF patients with lean compared to obese polycystic ovarian syndrome (PCOS) phenotypes. Design: A retrospective cohort study of patients with PCOS who underwent IVF in a single, academically affiliated infertility center in the USA between December 2014 and July 2020. The diagnosis of PCOS was assigned based on Rotterdam criteria. Patients were designated as lean (< 25) or overweight/obese (≥ 25) PCOS phenotype based on BMI (kg/m2) at cycle start. Baseline clinical and endocrinologic laboratory panel, cycle characteristics, and reproductive outcomes were analyzed. The cumulative live birth rate included up to 6 consecutives cycles. A Cox proportional hazards model and Kaplan–Meier curve for estimating live birth rates were used to compare the two phenotypes. Results: A total of 1395 patients who underwent 2348 IVF cycles were included. The mean (SD) BMI was 22.7 (2.4) in the lean and 33.8 (6.0) in the obese group (p < 0.001). A number of endocrinological parameters were similar between lean and obese phenotypes: total testosterone 30.8 ng/dl (19.5) vs 34.1 (21.9), p > 0.02 and pre-cycle hemoglobin A1C 5.33% (0.38) vs 5.51% (0.51) p > 0.001, respectively. The CLBR was higher in those with a lean PCOS phenotype: 61.7% (373/604) vs 54.0% (764/1414) respectively. Miscarriage rates were significantly higher for O-PCOS patients (19.7% (214/1084) vs 14.5% (82/563) p < 0.001) and the rate of aneuploids was similar (43.5%, 43.8%, p = 0.8). A Kaplan–Meier curve estimating the proportion of patients with a live birth was higher in the lean group (log-rank test p = 0.013). After adjusting for potential confounders, the lean phenotype was associated with an increased hazard ratio for live birth: HR = 1.38 p < 0.001. Conclusions: Lean PCOS phenotype is associated with a significantly higher CLBR compared to their obese counterparts. Miscarriage rates were significantly higher among obese patients, despite comparable pre-cycle HBA1C and similar aneuploidy rates in patients who underwent PGT-A. [ABSTRACT FROM AUTHOR]

• This novel machine-learning algorithm demonstrates oocyte maturation rate prediction ability in IVF/ICSI protocols. • Application of machine learning allows for the integration of multiple parameters. • A machine learning algorithm for oocyte maturation prediction allows for development of a prognostic tool before final trigger for ovulation and retrieval. Oocyte maturation is affected by various patient and cycle parameters and has a key effect on treatment outcome. A prediction model for oocyte maturation rate formulated by using machine learning and neural network algorithms has not yet been described. A retrospective cohort study that included all women aged ≤ 38 years who underwent their first IVF treatment using a flexible GnRH antagonist protocol in a single tertiary hospital between 2010 and 2015. 462 patients met the inclusion criteria. Median maturation rate was approximately 80%. Baseline characteristics and treatment parameters of cycles with high oocyte maturation rate (≥80%, n = 236) were compared to cycles with low oocyte maturation rate (<80%, n = 226). We used an XGBoost algorithm that fits the training data using decision trees and rates factors according to their influence on the prediction. For the machine training phase, 80% of the cohort was randomly selected, while rest of the samples were used to evaluate our model's accuracy. We demonstrated an accuracy rate of 75% in predicting high oocyte maturation rate in GnRH antagonist cycles. Our model showed an operating characteristic curve with AUC of 0.78 (95% CI 0.73–0.82). The most predictive parameters were peak estradiol level on trigger day, estradiol level on antagonist initiation day, average dose of gonadotropins per day and progesterone level on trigger day. A state-of-the-art machine learning algorithm presented promising ability to predict oocyte maturation rate in the first GnRH antagonist flexible protocol using simple parameters before final trigger for ovulation. A prospective study to evaluate this model is needed. [ABSTRACT FROM AUTHOR]

Backgroud: Several studies showed that human papillomavirus (HPV) affects male fertility, but its impact on female fertility and in vitro fertilization (IVF) outcome is not yet clear. Methods: Objective of this observational, prospective, cohort study was to evaluate the prevalence of HPV infection in women candidate to IVF, and the effects of HPV infection on the kinetic of embryonic development and on IVF outcome. A total number of 457 women candidate to IVF were submitted to HR-HPV test; among them, 326 underwent their first IVF cycle and were included in the analysis on IVF results. Results: 8.9% of women candidate to IVF were HPV-positive, HPV16 being the most prevalent genotype. Among the infertility causes, endometriosis was significantly more frequent in HPV-positive than in negative women (31.6% vs. 10.1%; p < 0.01). Granulosa and endometrial cells resulted HPV-positive in 61% and 48% of the women having HPV-positive cervical swab, respectively. Comparing HPV-positive and negative women at their first IVF cycle, no significant difference was observed in the responsiveness to controlled ovarian stimulation (COS) in terms of number and maturity of retrieved oocytes, and of fertilization rate. The mean morphological embryo score was comparable in the two groups; embryos of HPV-positive women showed a quicker development in the early stages, with a significantly shorter interval between the appearance of pronuclei and their fusion. In the following days, embryo kinetic was comparable in the two groups until the early blastocyst stage, when embryos of HPV-positive women became significantly slower than those of HPV-negative women. Overall, these differences did not affect live birth rate/started cycle, that was comparable in HPV-positive and negative women (22.2 and 28.1%, respectively). Conclusions: (a) the prevalence of HPV infection in women candidate to IVF is similar to that observed in the general female population of the same age range; (b) HPV infection migrates along the female genital apparatus, involving also the endometrium and the ovary, and perhaps participates in the genesis of pelvic endometriosis; (c) HPV slightly affects the developmental kinetic of in vitro-produced embryos, but does not exert an effect on live birth rate. [ABSTRACT FROM AUTHOR]

Embryo selection in in vitro fertilization-embryo transfer (IVF-ET) mostly relies on morphological assessment using a conventional microscope or the time-lapse monitoring system, which is not comprehensive. Inappropriate levels of reactive oxygen species (ROS) in the fertilization medium may cause damage to gametes, eventually leading to adverse IVF outcomes. The present study aimed to identify the optimal oxidation-reduction level in the fertilization medium for IVF outcomes by measuring the static oxidation-reduction potential (sORP) using a highly accurate and sensitive MiOXSYS system. A total of 136 patients undergoing IVF following brief incubation were divided equally into 4 groups in this prospective cohort study. The sORP value in the fertilizationmedium was detected using the MiOXSYS system, and its relationship with IVF outcomes was analyzed. The primary outcome was pregnancy outcomes, including live birth rate (LBR), clinical pregnancy rate (CPR), biochemical pregnancy rate (BPR), and implantation rate (IR). The secondary outcome was embryo quality, including fertilization rate (FR), cleavage rate (CR), available embryo rate (AER), and good-quality embryo rate (GQER). Group II (sORP: 228.7-235.3 mV) showed a higher LBR, CPR, BPR, and IR compared with Group III (sORP: 235.4-242.7 mV), presented as follows: LBR (32.0% for Group II vs 3.6% for Group III, P = 0.033), CPR (32.0% for Group II vs 3.6% for Group III, P = 0.033), BPR (36.0% for Group II vs 3.6% for Group III, P = 0.019), and IR (31.3% for Group II vs 2.7% for Group III, P = 0.003). The FR in Groups I and II had lower significant differences compared with that in Groups III and IV (71.7% and 70.3% for Groups I and II vs 83.5% and 80.4% for Groups III and IV, P = 0.000). The GQER in Group I to Group IV was 32.7%, 37.4%, 26.5%, and 33.3%, respectively (P = 0.056). This study indicated that the sORP value in the fertilization medium might be a potential indicator of embryo quality and pregnancy outcome. [ABSTRACT FROM AUTHOR]

Objectives: To find out the occurrence of ovarian hyperstimulation in patients who were hyper responders in in vitro fertilization cycles. The secondary outcome was to assess the number of metaphase II oocyte and fertilization rate, cleavage rate and pregnancy outcome when GnRHa is used for final maturation and triggering ovulation. STUDY DESIGN, SIZE, and DURATION: This is a retrospective descriptive analysis of cases managed at single center from June 2017 till May 2018. PATIENTS & METHODS: Twenty patients were identified as hyper responders based on baseline, ovarian reserve characteristics, that is antral follicle count, (AFC) > 25, AMH > 4ng/ml and on day of trigger, follicles >- 25 in number of ≥ 11mm were administered GnRHa trigger and 1500IU hCG on oocyte retrieval day while luteal phase was supported with daily vaginal progesterone and twice daily estradiol valerate. Sixteen patients underwent fresh transfer while four patients had their embryos frozen. MAIN RESULTS: Twenty patients were identified as high risk and their baseline characteristics were, mean age 31.7 ± 4.50, mean antral follicle count 25.7 ± 5.01, Anti Mullerian hormone level mean 4.64 ± 2.52 and PCOS was present in 35% cases. Peak estradiol level mean 13455-± 6632pmol/l and mean follicles count of 25.45 ± 8.78 confirmed a high response. The oocyte yield was 11.45+ Metaphase oocyte retrieved were 85.5% and cleavage rate of 93%. No case of early-onset OHSS was identified. Only one patient developed moderate OHSS. The pregnancy rate was 31.25%. The miscarriage rate was 6.3% and ongoing pregnancy was 25%. CONCLUSION: This small retrospective descriptive analysis supports the view of current literature that GnRH trigger not only prevents early onset OHSS also achieves increase of M11 oocytes. In addition, pregnancy outcome is not statistically different to those cycles where hCG is used as trigger. [ABSTRACT FROM AUTHOR]

Abstract Background Our objective was to investigate the existence of an optimal period for oocyte retrieval in regards to the clinical pregnancy occurrence after the administration of recombinant human chorionic gonadotropin (rhCG) (Ovitrelle®). Methods We studied the digital records of 3362 middle eastern couples who underwent in vitro fertilization (IVF) treatment between 2019 and 2021. Results Through statistical testing, we found that there is a significant positive correlation between the oocyte retrieval period and the clinical pregnancy occurrence up to the 37th hour, where retrieval at the 37th hour was found to provide the most optimal outcome, especially in the case of gonadotropin-releasing hormone agonist (GnRHa) long protocol. Conclusions This cohort study recommends retrieval at hour 37 after ovulation triggering under the described conditions.

Abstract Background This study aimed to evaluate the influences of SARS-CoV-2 infection on semen parameters and investigate the impact of the infection on in vitro fertilization (IVF) outcomes. Methods This retrospective study enrolled couples undergoing IVF cycles between May 2020 and February 2021 at Tongji Hospital, Wuhan. Baseline characteristics were matched using propensity score matching. Participants were categorized into an unexposed group (SARS-COV-2 negative) and exposed group (SARS-COV-2 positive) based on a history of SARS-CoV-2 infection, and the populations were 148 and 50 after matching, respectively. IVF data were compared between the matched cohorts. Moreover, semen parameters were compared before and after infection among the infected males. The main measures were semen parameters and IVF outcomes, including laboratory and clinical outcomes. Results Generally, the concentration and motility of sperm did not significantly differ before and after infection. Infected males seemed to have fewer sperm with normal morphology, while all values were above the limits. Notably, the blastocyst formation rate and available blastocyst rate in the exposed group were lower than those in the control group, despite similar mature oocytes rates, normal fertilization rates, cleavage rates, and high-quality embryo rates. Moreover, no significant differences were exhibited between the matched cohorts regarding the implantation rate, biochemical pregnancy rate, clinical pregnancy rate, or early miscarriage rate. Conclusions The results of this retrospective cohort study suggested that the semen quality and the chance of pregnancy in terms of IVF outcomes were comparable between the males with a history of SARS-CoV-2 infection and controls, although a decreased blastocyst formation rate and available blastocyst rate was observed in the exposed group, which needs to be reinforced by a multicenter long-term investigation with a larger sample size.

Background: Intracytoplasmic sperm injection (ICSI) has become a common method of fertilization in assisted reproduction worldwide. However, there are still gaps in knowledge of the ideal IVF-ICSI workflow including the optimal duration of time between induction of final oocyte maturation, oocyte denudation and ICSI. The aim of this study was to examine outcomes following different workflow protocols in IVF-ICSI procedures in blastocysts that have undergone undisturbed incubation and preimplantation genetic testing for aneuploidy (PGT-A) prior to transfer. Methods: Retrospective secondary analysis of 113 patients (179 IVF cycles, 713 embryos), all of whom have gone through IVF-ICSI and PGT-A using undisturbed culture. Predictive test variables were the length of time from: trigger to OPU, OPU to denudation, and denudation to ICSI. Outcome metrics assessed were: maturation, fertilization, blastulation and euploid rates. Generalized Estimated Equations Linear Model was used to examine the relationship between key elements of a given cycle and continuous outcomes and LOESS curves were used to determine the effect over time. Results: In a paired multi-regression analysis, where each patient served as its own control, delaying OPU in patients with unexplained infertility improved both maturation and blastulation rates (b = 29.7, p < 0.0001 and b = 9.1, p = 0.06, respectively). Longer incubation with cumulus cells (CCs) significantly correlated with improved ploidy rates among patients under 37, as well as among patients with unexplained infertility (r = 0.22 and 0.29, respectively), which was also evident in a multiple regression analysis (b = 6.73, p < 0.05), and in a paired analysis (b = 6.0, p < 0.05). Conversely, among patients with a leading infertility diagnosis of male factor, longer incubation of the denuded oocyte prior to ICSI resulted in a significantly higher euploid rate (b = 15.658, p < 0.0001). Conclusions: In this study we have demonstrated that different IVF-ICSI workflows affect patients differently, depending on their primary infertility diagnosis. Thus, ideally, the IVF-ICSI workflow should be tailored to the individual patient based on the primary infertility diagnosis. This study contributes to our understanding surrounding the impact of IVF laboratory procedures and highlights the importance of not only tracking "classic" IVF outcomes (maturation, fertilization, blastulation rates), but highlights the importance that these procedures have on the ploidy of the embryo. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate six vaginal douching agents (Iodine, Saline, Iodine followed by saline, chlorhexidine acetate followed by saline, Ozone, Potassium permanganate) on oocytes pick-up related pelvic infection (OPU-PI) and IVF outcome in patients underwent assisted reproduction technology (ART). Design: Through searching PubMed, Embase, Cochrane Library, Web of Science, Ovid, CINAHL CNKI, only human clinical trials were collected to study the effects of the six vaginal douching agents on OPU-PI and IVF outcomes. The included studies were evaluated for methodological quality by the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly. Results: The clinical trials were collected between the earliest available date and June 2022. Eight studies were included, the total sample size used in the study was 12,567. The results of the network meta-analysis showed that Ozone can significantly decrease OPU-PI; Iodine followed by saline can be a antiseptic protocol ranked first without affecting the quality of oocytes and Chlorhexidine acetate followed by saline can improve patients’ clinical pregnancy rate. Conclusion: Based on Ranking Plot of the Network, this review reports the best evidence available regarding different vaginal douching agents used before OPU. [ABSTRACT FROM AUTHOR]

Background: The cryopreservation of sperm or embryos has been an important strategy in the treatment of infertility. Recently studies have revealed the outcomes after IVF (in vitro fertilization) treatment for single-factor exposure either to frozen sperm or embryos.Methods: This retrospective study was to uncover the exposure to both frozen sperm and embryo effects using IVF/H (in vitro fertilization using husbands' fresh sperm) or IVF/D (in vitro fertilization using donors' frozen sperm) treatment.Results: The results showed the clinical pregnancy rate (CPR), live birth rate (LBR) and low birth weight rate (LBW) increased to 63.2% (or 68.1%), 61.1% (or 66.4%) and 15.8% (or 16.2%) after using frozen embryo transfer within Group IVF/H (or Group IVF/D). After using frozen sperm, the high-quality embryo rate (HER) increased to 52% and baby with birth defect rate (BDR) reduced to 0% in subgroup D/ET comparing to subgroup H/ET. While the fertilization rate (FER), cleavage rate (CLR), HER and multiple pregnancy rate (MUR) reduced to 75%, 71%, 45% and 9.2% in subgroup D/FET comparing to subgroup H/FET. Finally, our study found accumulative frozen gamete effects, including both sperm and embryos, led to the significantly increasing in the HER (p < 0.05), CPR (p < 0.001), LBR (p < 0.001) and LBW (p < 0.05) in subgroup D/FET comparing to subgroup H/ET.Conclusion: The use of frozen embryos and frozen sperm have complementary IVF outcomes. Our findings highlighted the parent's distinguished frozen effect not only for clinical studies but also for basic research on the mechanism of cellular response adaptations to cryopreservation. [ABSTRACT FROM AUTHOR]

Purpose: Despite advances in IVF techniques, determining the prognostic factors influencing cumulative live birth rate (CLBR) remains crucial for optimizing outcomes. Among the various key performance indicators in the lab, blastulation rate, and more specifically Total Blastocyst Usable Rate (TBUR), has gained particular interest. In this study we aimed at determining if TBUR was significantly associated with CLBR., Basic Procedures: This monocentric retrospective case-control study was conducted in 317 consecutive IVF/ICSI cycles in 2014-2020 and leading to the formation of 3 usable blastocysts, including freeze all cycles. TBUR (usable blastocysts / 2PNs) was calculated and CLBR after 2-year follow up was recorded, including both fresh and frozen embyro transfers. CLBR was then compared between 2 groups according to TBUR (group 1: TBUR ≥50 % vs group 2: TBUR ≤30 %)., Main Findings: CLBR was significantly higher in group 1 than in group 2 (57 vs. 41 %, p = 0.02). Adjusted logistic regression showed a statistically significant relationship between CLBR and TBUR, with a significantly lower chance of achieving a live birth in group 2 than in group 1 (OR = 0.408 [0.17-0.96]; p = 0.04)., Principal Conclusions: Although the monocentric design and the arbitrary choice of thresholds for TBUR and number of blastocysts call for caution when generalizing the findings and advocates for external validation, our results illustrate that TBUR is a valuable prognostic factor of CLBR in IVF cycles which might serve as a tool for lab monitoring, cycle analysis by medical staff and patients' counselling. These results fit well within the P4 medicine concept (Predictive, Preventive, Personalized, and Participatory), and advocate for further research in order to improve embryo culture conditions., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

This systematic review and meta-analysis aims to evaluate the impact of chronic endometritis (CE) and its therapy on in vitro fertilization (IVF) outcome. Additionally, we aim to investigate whether various degrees of CE severity may exert a different effect on IVF outcome. Ongoing-pregnancy rate/live-birth-rate (OPR/LBR), clinical-pregnancy rate (CPR), and miscarriage rate (MR) were calculated. A total number of 4145 patients (from ten studies) were included. Women with CE had lower OPR/LBR (OR 1.97, p = 0.02) and CPR (OR 2.28, p = 0.002) compared to those without CE. CE cure increased OPR/LBR (OR 5.33, p < 0.0001) and CPR (OR 3.64, p = 0.0001). IVF outcome was comparable between women with cured CE and those without CE (OPR/LBR, CPR and MR: p = ns). Women with severe CE had lower OPR/LBR (OR 0.43, p = 0.003) and CPR (OR 0.40, p = 0.0007) compared to those mild CE. Mild CE showed no influence on the IVF outcome as compared to women without CE (OPR/LBR, CPR and MR: p = ns). Based on this data analysis, CE significantly reduces OPR/LBR and CPR in women undergoing IVF. Importantly, CE resolution after antibiotic therapy may improves IVF outcome, leading to similar OPR/LBR and CPR as compared to unaffected patients. The negative effects of CE on IVF outcome may be restricted to severe disease, whereas mild CE may have no influence on IVF success. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to assess the in vitro fertilization (IVF) treatments outcomes of women with recurrent implantation failure (RIF) after hysteroscopic isthmoplasty for isthmocele. Methods: This retrospective, observational study included 61 patients with RIF and isthmocele who presented to IVF Unit of Hüma Obstetrics and Gynecology Hospital between January, 2018 and December, 2020. Thirty‐one patient who underwent hysteroscopic isthmoplasty—before IVF procedure—were included. Remaining 30 patients underwent IVF without hysteroscopic isthmoplasty were included as controls. The fertility outcome were compared between groups. Results: After 3 months, spontaneous pregnancy was achieved in 18.4% (7/38) of patients with isthmocele who underwent hysteroscopic isthmoplasty. In the isthmoplasty group, implantation rate, clinical pregnancy rate, biochemical pregnancy rate, and the miscarriage rate were 41.9% (13/31), 35.5% (11/31), 6.5% (2/31), and 9.7% (3/31), respectively. The live birth rate after in vitro fertilization was 25.8% (8/31) in the isthmoplasty group and 3.3% (1/30) in the control group (p < 0.05). There were no significant differences in the IVF outcomes such as the biochemical pregnancy rate and miscarriage rate between the isthmoplasty and control groups. Conclusion: This study demonstrated that hysteroscopic isthmoplasty improves pregnancy and live birth rates for women with a history of RIF and isthmocele. Reproductive results of the IVF cycles after hysteroscopic correction of isthmocele were comparable to those of the patients without any uterine abnormalities and those with diagnosis of unexplained infertility. [ABSTRACT FROM AUTHOR]

It has been long-known that endometrium-secreted cytokines play a critical role during embryo implantation. However, whether cytokines secreted from the embryo are relevant to the process of embryo implantation remains unclear. The concentration of cytokines in embryo culture medium was tested using a newly developed, high-sensitivity single-cell proteomic platform and evaluated in comparison to embryo quality and clinical outcome. The effect of TNF-α on embryo and endometrium Ishikawa cells was investigated using immunofluorescence staining, CCK-8 assay, TUNEL staining, and RT-qPCR. Of the 10 cytokines measured, only TNF-α concentration was significantly higher in the group with embryo implantation failure. Immunofluorescence staining showed that the expression of TNF-α was unevenly distributed in blastocysts, and the expression level was significantly correlated with the blastocyst inner cell mass (ICM) quality score. Gene profiling showed that addition of TNF-α led to increased expression of tumor necrosis factor receptor 1 (TNFR1) and apoptosis-related genes and that this could be inhibited by the TNF-α receptor inhibitor etanercept (ETA). In addition, an increased expression of water and ion channels, including AQP3, CFTR, ENaCA, and CRISP2 was also observed which could also be inhibited by ETA. Our results show that higher embryo-secreted TNF-α levels are associated with implantation failure through activation of TNF-α receptor, and TNF-α may be an independent predictor for pre-transfer assessment of the embryo development potential in IVF patients. [ABSTRACT FROM AUTHOR]

We retrospectively studied a real-life population of 1470 women undergoing IVF, with poor/suboptimal/normal ovarian responsiveness to controlled ovarian stimulation (COS), comparing the cumulative live birth rate (cLBR) when COS was performed using rFSH alone or rFSH + rLH in a 2:1 ratio. Overall, we observed significantly higher cLBR in the rFSH alone group than in the rFSH + rLH group (29.3% vs. 22.2%, p < 0.01). However, considering only suboptimal/poor responders (n = 309), we observed comparable cLBR (15.6% vs. 15.2%, p = 0.95) despite the fact that patients receiving rFSH + rLH had significantly higher ages and worse ovarian reserve markers. The equivalent effectiveness of rFSH + rLH and rFSH alone was further confirmed after stratification according to the number of oocytes retrieved: despite basal characteristics were still in favor of rFSH alone group, the cLBR always resulted comparable. Even subdividing patients according to the POSEIDON classification, irrespective of differences in the baseline clinical characteristics in favor of FSH alone group, the cLBR resulted comparable in all subgroups. Despite the retrospective, real-life analysis, our data suggest that rLH supplementation in COS may represent a reasonable option for patients with predictable or unexpected poor/suboptimal ovarian responsiveness to FSH, those matching the Bologna criteria for poor responsiveness, and those included in the POSEIDON classification. [ABSTRACT FROM AUTHOR]

Background: Our objective was to investigate the existence of an optimal period for oocyte retrieval in regards to the clinical pregnancy occurrence after the administration of recombinant human chorionic gonadotropin (rhCG) (Ovitrelle®).Methods: We studied the digital records of 3362 middle eastern couples who underwent in vitro fertilization (IVF) treatment between 2019 and 2021.Results: Through statistical testing, we found that there is a significant positive correlation between the oocyte retrieval period and the clinical pregnancy occurrence up to the 37th hour, where retrieval at the 37th hour was found to provide the most optimal outcome, especially in the case of gonadotropin-releasing hormone agonist (GnRHa) long protocol.Conclusions: This cohort study recommends retrieval at hour 37 after ovulation triggering under the described conditions. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the influences of SARS-CoV-2 infection on semen parameters and investigate the impact of the infection on in vitro fertilization (IVF) outcomes. Methods: This retrospective study enrolled couples undergoing IVF cycles between May 2020 and February 2021 at Tongji Hospital, Wuhan. Baseline characteristics were matched using propensity score matching. Participants were categorized into an unexposed group (SARS-COV-2 negative) and exposed group (SARS-COV-2 positive) based on a history of SARS-CoV-2 infection, and the populations were 148 and 50 after matching, respectively. IVF data were compared between the matched cohorts. Moreover, semen parameters were compared before and after infection among the infected males. The main measures were semen parameters and IVF outcomes, including laboratory and clinical outcomes. Results: Generally, the concentration and motility of sperm did not significantly differ before and after infection. Infected males seemed to have fewer sperm with normal morphology, while all values were above the limits. Notably, the blastocyst formation rate and available blastocyst rate in the exposed group were lower than those in the control group, despite similar mature oocytes rates, normal fertilization rates, cleavage rates, and high-quality embryo rates. Moreover, no significant differences were exhibited between the matched cohorts regarding the implantation rate, biochemical pregnancy rate, clinical pregnancy rate, or early miscarriage rate. Conclusions: The results of this retrospective cohort study suggested that the semen quality and the chance of pregnancy in terms of IVF outcomes were comparable between the males with a history of SARS-CoV-2 infection and controls, although a decreased blastocyst formation rate and available blastocyst rate was observed in the exposed group, which needs to be reinforced by a multicenter long-term investigation with a larger sample size. [ABSTRACT FROM AUTHOR]

Endometriosis (EM) affects 10% women of reproductive age and alters fertility. Its management is still debated notably the timing of surgery and ART in infertility. Kallistatin (KS) is an endogenous protein that regulates differential signaling pathways and biological functions. However, the function and the underlying molecular mechanism in EM and its correlation with in vitro fertilization (IVF) outcome have not been determined. The purpose of this study was to evaluate KS concentrations in follicular fluid (FF) of women with EM and controls women without EM who underwent IVF with embryo transfer (IVF–ET). FF KS concentrations from 40 patients with EM and 40 non-EM patients were measured by ELISA. Compared with the non-EM patients, patients with EM had lower KS levels in FF (281.67 ± 104.60 vs. 490.70 ± 216.33 pg/ml). The rates of fertilization (61.64 ± 22.42 vs. 71.00 ± 24.39%), available embryo (45.96 ± 19.83 vs. 50.61 ± 26.26%), and top-quality embryo (12.71 ± 21.01 vs. 16.04 ± 16.87%) were significantly lower in the EM group than in the control group. The KS concentrations in the FF of women who conceived consequent to the treatment were significantly higher than those from women who did not in the combined EM and control groups. These results indicate that the KS concentration in FF could be used as a predictor for IVF–ET outcomes. This may contribute to the pathologic mechanism responsible for the poor outcome of IVF in patients with EM. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the effects of insulin resistance (IR) on IVF outcomes and a potential underlying mechanism in lean women without PCOS.DesignA prospective cohort study at the University Clinic.SettingIVF center at the University setting.PatientsA total of 155 lean women (body mass index

To assess the relation between oocytes yield including total retrieved oocytes (O)c and total mature oocytes (MII) relative to the antral follicular count (AFC) (3–9 mm in diameter) and relative to anti-müllerian hormone (AMH) ng/mL level: Oc/AFC, MII/AFC, Oc/AMH, and MII/AMH, respectively, and ART outcomes. We included retrospectively 264 IVF cycles after the first embryo transfer (ET) and after the cumulative ET (CET). The implantation rate (IR) and the live birth rate (LBR) after first ET were 31 ± 39% and 32.6%, respectively, and after CET 35 ± 38% and 45.1%, respectively. There was a significantly higher average of Oc/AFC and MII/AFC when live birth (LB) occurred after the first ET (0.82 ± 0.4 vs. 0.71 ± 0.35 and 0.57 ± 0.4 vs. 0.68 ± 0.3, respectively, P < 0.05). We reported a significantly higher average of MII/AFC when LB occurred after CET (0.66 ± 0.3 vs. 0.56 ± 0.30, P = 0.02) in comparison to the group where no LB was obtained. Increased Oc/AFC and MII/AFC ratios were associated with the occurrence of LB and increased IR after first ET (P < 0.05). Increased MII/AFC ratio was associated with the occurrence of LB and IR after CET (P = 0.02 and P = 0.04, respectively). After age-adjusted multivariate analyses, all these trends were confirmed (P < 0.05) except for the effect of MII/AFC ratio on IR after CET. In conclusion, Oc/AMH and MII/AMH ratios have no effect on the occurrence of LBR or on IR after first ET or CET at either age grouping. Ratios Oc/AFC and MII/AFC seem promising indicators to assess ovarian response.

Background: The current study aimed to investigate the impact of asymptomatic or mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on female fertility and laboratory and clinical outcomes in assisted reproductive technology (ART) treatments.Methods: Patients undergoing ART treatments in the Reproductive Medicine Center, Tongji Hospital, Wuhan, from May 2020 to February 2021 were enrolled. Seventy of them were positive for serum SARS-CoV-2 antibodies (IgG and/or IgM), and 3973 patients had negative results. Propensity score matching with a ratio of 1:3 was performed, and there were 65 females in the case group and 195 females in the control group.Findings: The ovarian reserves and ovarian responses between groups after matching were similar. The proportions of mature oocytes, damaged oocytes, fertilized oocytes, cleavage embryos, high-quality embryos, and available blastocysts were also similar, despite a slight decrease in the blastocyst formation rate in the case group. In addition, there were no significant differences in terms of the biochemical pregnancy rate, clinical pregnancy rate, early miscarriage rate, or implantation rate.Interpretation: There is no evidence that a history of asymptomatic or mild SARS-CoV-2 infection in females may negatively affect female fertility, embryo laboratory outcomes, or clinical outcomes in ART treatments. Funding: This study was supported by the National Key Research and Development Project (2018YFC1002103) and the Health Commission of Hubei Province Scientific Research Project (WJ2021M110).

Objective: To investigate the effects of insulin resistance (IR) on IVF outcomes and a potential underlying mechanism in lean women without PCOS. Design: A prospective cohort study at the University Clinic. Setting: IVF center at the University setting. Patients: A total of 155 lean women (body mass index <25) without PCOS undergoing IVF cycle. Intervention: Patients were allocated to IR and non-IR groups based on HOMA-M120. Main Outcome Measure(s): IVF outcomes, including egg quality, the percentage of mature oocytes, fertilization rate, blastocyst formation rate, advanced embryo rate, and cumulative live birth rate were investigated. Auto-immune parameters, peripheral blood immunophenotypes, thyroid hormone, homocysteine, and 25-OH-vitamin D3 (25-OH-VD3) levels were analyzed. Results: The percentage of mature oocytes and blastocyst formation rate were significantly lower in the IR group as compared with those of the non-IR group (p<0.05, respectively). The proportion of peripheral blood CD19+ B cells was significantly higher in the IR group than those of the non-IR group (p<0.05). Homocysteine, 25-OH-VD3, and auto-immune parameters were the same between the two groups. Conclusion: In lean infertile women without PCOS, IR is associated with the decreased percentage of mature eggs and poor embryo quality in which B cell immunity may play a role. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Has cumulative live birth rate (CLBR) improved over time and which factors are associated with such an improvement? SUMMARY ANSWER During an 11-year period, 2007–2017, CLBR per oocyte aspiration increased significantly, from 27.0% to 36.3%, in parallel with an increase in blastocyst transfer and cryopreservation by vitrification. WHAT IS KNOWN ALREADY While it has been shown that live birth rate (LBR) per embryo transfer (ET) is higher for fresh blastocyst than for fresh cleavage stage embryo transfer, CLBR per oocyte aspiration, including one fresh ET and all subsequent frozen embryo transfers (FET), does not seem to differ between the two culture strategies. STUDY DESIGN, SIZE, DURATION A national register study including all oocyte aspirations performed in Sweden from 2007 to 2017 (n = 124 700 complete IVF treatment cycles) was carried out. Oocyte donation cycles were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS Data were retrieved from the Swedish National Registry of Assisted Reproduction (Q-IVF) on all oocyte aspirations during the study period where autologous oocytes were used. CLBR was defined as the proportion of deliveries with at least one live birth per oocyte aspiration, including all fresh and/or frozen embryo transfers within 1 year, until one delivery with a live birth or until all embryos were used, whichever occurred first. The delivery of a singleton, twin, or other multiples was registered as one delivery. Cryopreservation of cleavage stage embryos was performed by slow freezing and of blastocyst by vitrification. MAIN RESULTS AND THE ROLE OF CHANCE In total, 124 700 oocyte aspirations were performed (in 61 313 women), with 65 304 aspirations in women <35 years and 59 396 in women ≥ 35 years, resulting in 38 403 deliveries with live born children. Overall, the CLBR per oocyte aspiration increased significantly during the study period, from 27.0% to 36.3% (odds ratio (OR) 1.039, 95% CI 1.035–1.043) and from 30.0% to 43.3% if at least one ET was performed (adjusted OR 1.055, 95% CI 1.050–1.059). The increase in CLBR was independent of maternal age, number of oocytes retrieved and number of previous IVF live births. The CLBR for women <35 and ≥35 years both increased significantly, following the same pattern. During the study period, a substantially increasing number of blastocyst transfers was performed, both in fresh and in FET cycles. Other important predicting factors for live birth, such as number of embryos transferred, could not explain the improvement. An increased single embryo transfer rate was observed with time. LIMITATIONS, REASONS FOR CAUTION The retrospective design implicates that other confounders of importance for CLBR cannot be ruled out. In addition, some FET cycles might be performed later than 1 year post oocyte aspiration for the last year (2017) and are, thus, not included in this study. In addition, no data on 'dropouts', i.e. patients that do not continue their treatment despite having cryopreserved embryos, are available, or if this drop-out rate has changed over time. WIDER IMPLICATIONS OF THE FINDINGS The results suggest that blastocyst transfer, particularly when used in FET cycles and in combination with vitrification, is an important contributor to the improved live birth rates over time. This gives a possibility for a lower number of oocyte aspirations needed to achieve a live birth and a shortened time to live birth. STUDY FUNDING/COMPETING INTERESTS The study was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70940) and by Hjalmar Svensson's research foundation. None of the authors declares any conflict of interest. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the effect of melatonin supplementation on the outcomes of in vitro fertilization (IVF) and mitochondrial adenosine triphosphate production (MT-ATP6) gene expression in Iranian infertile couples. A single-blind nonrandomized controlled trial was conducted, recruiting 90 infertile couples who underwent IVF at an infertility center in Tehran, Iran. Patients who were assigned to the intervention group received melatonin as a supplementation to the standard controlled ovarian stimulation (COS). The control group received a COS protocol only. Primary outcome was the mRNA level of the MT-ATP6 gene in cumulus cells of ovarian follicles. Secondary outcomes were the mean number of mature oocytes retrieved, the embryo quality, and biochemical and clinical pregnancy rates. The mRNA level of the MT-ATP6 gene in cumulus cells between intervention and control groups was not statistically different (0.931 vs.1; P ˃ 0.05). The mean number of poor-quality embryos was significantly lower in the intervention group than that in the control group (0.27 vs. 0.80; P = 0.028). The biochemical and clinical pregnancy rates were higher in the intervention group (24% vs. 14%, P = 0.089, and 14% vs. 7%, P = 0.302, respectively); however, the difference was not significant. Melatonin supplementation did not increase the odds of clinical pregnancy and the number of mature oocytes retrieved, but significantly reduced the number of low-quality embryos. More extensive studies focusing on the level of MT-ATP6 gene expression in the oocyte or blastomere cells may further elucidate the effect of supplementation with melatonin in infertile couples who have poor clinical outcomes. Trial registration: Current Controlled Trials: IRCT2015042912307N4. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aims to evaluate the impact of chronic endometritis (CE) and its therapy on in vitro fertilization (IVF) outcome. Additionally, we aim to investigate whether various degrees of CE severity may exert a different effect on IVF outcome. Ongoing-pregnancy rate/live-birth-rate (OPR/LBR), clinical-pregnancy rate (CPR), and miscarriage rate (MR) were calculated. A total number of 4145 patients (from ten studies) were included. Women with CE had lower OPR/LBR (OR 1.97, p = 0.02) and CPR (OR 2.28, p = 0.002) compared to those without CE. CE cure increased OPR/LBR (OR 5.33, p < 0.0001) and CPR (OR 3.64, p = 0.0001). IVF outcome was comparable between women with cured CE and those without CE (OPR/LBR, CPR and MR: p = ns). Women with severe CE had lower OPR/LBR (OR 0.43, p = 0.003) and CPR (OR 0.40, p = 0.0007) compared to those mild CE. Mild CE showed no influence on the IVF outcome as compared to women without CE (OPR/LBR, CPR and MR: p = ns). Based on this data analysis, CE significantly reduces OPR/LBR and CPR in women undergoing IVF. Importantly, CE resolution after antibiotic therapy may improves IVF outcome, leading to similar OPR/LBR and CPR as compared to unaffected patients. The negative effects of CE on IVF outcome may be restricted to severe disease, whereas mild CE may have no influence on IVF success.

Objective: To study the association between ambient air pollutant exposure during the follicular phase and in vitro fertilization (IVF) outcomes. Design: A single-center retrospective analysis. Setting: Henan Province, China. Patients: Patients (n = 6659) living in Zhengzhou, Henan Province in central China who underwent their first IVF cycle at the First Affiliated Hospital of Zhengzhou University between 2013 and 2019 were included for analysis. Intervention: None. Main outcome measure: The relationships between PM2.5, PM10, and AQI (Air Quality Index) with IVF outcomes during the follicular phase (period I, 85 days before oocyte retrieval; period II, gonadotrophin start to oocyte retrieval). Results: Compared with the bottom tertile, exposure to the top PM2.5 and PM10 tertiles during period I was associated with decreased clinical pregnancy (PM2.5: adjusted odds ratio [OR], 0.838%, and 95% confidence interval [CI], 0.723 and 0.971; PM10: adjusted OR, 0.818%, and 95% CI, 0.705 and 0.950), and decreased live birth rate (PM2.5: adjusted odds ratio [OR], 0.852%, and 95% confidence interval [CI], 0.736 and 0.987; PM10: adjusted OR, 0.850%, and 95% CI, 0.733 and 0.986), and exposure to the top PM2.5 tertile during period II adversely affected clinical pregnancy and the live birth rate (adjusted OR, 0.824%, and 95% CI, 0.711 and 0.955; adjusted OR, 0.817%, and 95% CI, 0.706 and 0.945). Compared with the bottom PM10 tertile, exposure to the middle PM10 tertile in period II showed decreased clinical pregnancies and live births (adjusted OR, 0.844; 95% CI, 0.729 and 0.978, adjusted OR, 0.846; 95% CI, 0.731 and 0.979). The PM10 level during period II of the follicular phase tend to adversely affect live birth rate, but the tendency did not reach significance (P = 0.051). Conclusion: Exposure to PM2.5 and PM10 before oocyte retrieval has an adverse effect on IVF outcomes. Capsule: Exposure to PM2.5 and PM10 before oocyte retrieval has an adverse effect on IVF outcomes.

Objective: To assess the role of embryo secretome in modifying the molecular profile of glycodelin A (GdA) in endometrial organoids (ORG) mimicking the implantation window. To verify whether the use of embryo-conditioned culture medium at the time of the embryo transfer may increase in vitro fertilization outcome.Design: Molecular study with human endometrial ORG and embryo-conditioned culture medium. Retrospective study using prospectively recorded data.Setting: University hospital.Patient(s): For isolation and culture of endometrial glandular ORG, endometrial biopsy specimens from five white women of proven fertility undergoing laparoscopy for tubal sterilization. A total of 75 women undergoing intracytoplasmic sperm injection for tubal and/or male infertility factor.Interventions(s): In vitro fertilization.Main Outcome Measure(s): Pinopodes presence in human endometrial ORG. Glycodelin A expression profile by means of two-dimensional electrophoresis. In vitro fertilization outcome.Result(s): This in vitro study demonstrated that the treatment of endometrial ORG with the secretome of medium conditioned by the growing embryo increased the GdA relative abundance and induced a different glycoform pattern. Biochemical and clinical pregnancy rate significantly increased when the spent medium was loaded during the transfer (17.5% vs. 36.6% and 16.5% vs. 35.1%, respectively).Conclusion(s): This study demonstrated that the secretome of implanting embryos is able to induce the expression as well as to determine the relative abundance and the glycosilation profile of endometrial GdA, a protein having a key role in the embryo-endometrial cross talk. Moreover, a significant increase in pregnancy rate was observed when the embryo transfer was performed by using the culture medium conditioned by the growing embryo. [ABSTRACT FROM AUTHOR]

The impact of aging on reproductive outcomes has received considerable critical attention; however, there is much less information available on the effects of paternal age compared to the effects of maternal age. In this study, methylation levels of sperm rDNA promoter regions and Long Interspersed Nucleotide Element 1 (LINE-1) were measured using pyrosequencing and fertilization, day 3 good-quality embryo, pregnancies, and implantation results were assessed. We observed significantly increasing levels of DNA methylation in the sperm rDNA promoter regions with age based on stratifying the samples by age alone (P = 0.0001) and performing linear regression analysis (P < 0.0001). Meanwhile, no statistically significant correlations were observed between global LINE-1 methylation with age. No statistically significant correlations were observed between sperm rDNA promoter methylation levels and either the day 3 good-quality embryo rate or clinical pregnancy rate. In contrast, the correlation between sperm rDNA promoter methylation levels and fertilization (2 pronuclei) rate was nearly significant (P = 0.0707), especially the methylation levels of some individual CpG units (CpG_10, P = 0.0176; CpG_11, P = 0.0438; CpG_14, P = 0.0232) and rDNA promoter methylation levels measured using primerS2 (P = 0.0513). No significant correlation was found between sperm rDNA promoter methylation levels and fertilization rates (2 pronuclei, 1 pronuclei, and 1 polypronuclei). Our results demonstrate that sperm are susceptible to age-associated alterations in methylation levels of rDNA promoter regions, suggesting that sperm rDNA promoter methylation levels can be applied to DNA methylation-based age prediction, and that the aberrant methylation of rDNA promoters may be partially responsible for enhanced disease susceptibility of offspring sired by older fathers. Methylation levels of sperm rDNA promoter regions may correlate with polypronuclei rates of IVF programs.

The microbial contamination of the female genital tract has effect on the ivf outcome and negatively effect on fertility, fertilization and implantation rate. Lactobacillus sp. is the dominant organism of the vaginal flora that have an important role in the inhibition of pathogen. 48 patients were selected for this study aged between 20-40 years, During embryo transfer, 3 samples were collected from each patient from vagina, end cervical canal and the tip of the catheter. The samples were assayed microbiology. The microbial culture contained natural flora and pathogen organism .The isolated pathogens were identified as Klebsilla pneumonia, Escherichia coli, Candida albicans, C. tropicalis, C. famata, C. parapsilosis, C. catenulate according to Bergeyˊs manual and confirmed by VITEK System. Candida sp found to be the most frequent infemale genital tract. The probiotic (Lactobacillus. acidophilus) and its metabolites (bacteriocin) were inhibited growth of isolated pathogenic microbial in vitro.The result showed that L. acidophilus and their metabolite bacteriocin have antagonistic activity against pathogenic microbes. Recommendation: Oral or transvaginal administration of Lactobacillus or bacteriocin antiseptics; disinfected; maintain a health vagina and prevent the infection of the reproductive tract.

Objectives: The objectives of this study were (1) to assess the prevalence of ultrasound (US) features of adenomyosis in an infertile population undergoing in-vitro fertilization (IVF), (2) to define the inter- and intrarater agreement of three-dimensional (3D) US assessment of adenomyosis, and (3) to evaluate sonographic features of adenomyosis with respect to pregnancy outcome following transfer of a single thawed euploid blastocyst.Methods: This was a prospective cohort study. Subjects scheduled to undergo a single thawed euploid blastocyst transfer between April and December 2017 at a large IVF center were eligible for inclusion. Enrolled subjects underwent endometrial preparation for frozen embryo transfer. 3D-US was performed on the day prior to embryo transfer, with images stored for subsequent evaluation. Subjects then underwent transfer of a single thawed euploid blastocyst, and pregnancy outcomes were collected. All 3D-US volumes were de-identified and reviewed independently by five reproductive endocrinologists/infertility specialists with expertise in gynecological US for the presence of seven sonographic features of adenomyosis: global uterine enlargement, myometrial wall asymmetry, heterogeneous echogenicity, irregular junctional zone, myometrial cysts, fan-shaped shadowing and ill-defined myometrial lesions. Adenomyosis was considered to be present if the majority of the reviewers noted at least one of the seven sonographic features. Inter- and intrarater agreement was evaluated using Fleiss's kappa. Clinical and cycle characteristics of subjects with and those without adenomyosis were compared. The primary outcome of interest was live birth rate. Secondary outcomes included clinical pregnancy rate and miscarriage rate. Logistic regression analysis was performed to account for potential confounders.Results: A total of 648 subjects were included. The prevalence of adenomyosis on US was 15.3% (99/648). On retrospective chart review, very few patients with adenomyosis had symptoms. The inter- and intrarater agreement amongst five independent specialists conducting the 3D-US assessments of adenomyosis were poor (κ = 0.23) and moderate (κ = 0.58), respectively. Subjects with adenomyosis were older (37.1 vs 35.9 years, P = 0.02) and more likely to undergo a gonadotropin-releasing hormone agonist downregulation protocol when compared with those without adenomyosis (12.1% vs 5.1%, P = 0.02). Clinical pregnancy (80.0% vs 75.0%) and live birth (69.5% vs 66.5%) rates were similar between the groups. When adjusting for potential confounders, there was no difference in the rate of clinical pregnancy (adjusted odds ratio (aOR), 1.47 (95% CI, 0.85-2.56)), miscarriage (aOR, 1.3 (95% CI, 0.62-2.72)) or live birth (aOR, 1.28 (95% CI, 0.78-2.08)) between subjects with and those without adenomyosis. No individual sonographic marker of adenomyosis was predictive of pregnancy outcome.Conclusions: The inter-rater agreement of 3D-US assessment of adenomyosis is poor. Furthermore, sonographic markers of adenomyosis in asymptomatic patients may not be associated with altered pregnancy outcome following transfer of a single thawed euploid blastocyst. These findings suggest that routine screening for asymptomatic adenomyosis in an unselected infertile patient population undergoing frozen embryo transfer may not be warranted. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

The impact of aging on reproductive outcomes has received considerable critical attention; however, there is much less information available on the effects of paternal age compared to the effects of maternal age. In this study, methylation levels of sperm rDNA promoter regions and Long Interspersed Nucleotide Element 1 (LINE-1) were measured using pyrosequencing and fertilization, day 3 good-quality embryo, pregnancies, and implantation results were assessed. We observed significantly increasing levels of DNA methylation in the sperm rDNA promoter regions with age based on stratifying the samples by age alone (P = 0.0001) and performing linear regression analysis (P < 0.0001). Meanwhile, no statistically significant correlations were observed between global LINE-1 methylation with age. No statistically significant correlations were observed between sperm rDNA promoter methylation levels and either the day 3 good-quality embryo rate or clinical pregnancy rate. In contrast, the correlation between sperm rDNA promoter methylation levels and fertilization (2 pronuclei) rate was nearly significant (P = 0.0707), especially the methylation levels of some individual CpG units (CpG_10, P = 0.0176; CpG_11, P = 0.0438; CpG_14, P = 0.0232) and rDNA promoter methylation levels measured using primerS2 (P = 0.0513). No significant correlation was found between sperm rDNA promoter methylation levels and fertilization rates (2 pronuclei, 1 pronuclei, and 1 polypronuclei). Our results demonstrate that sperm are susceptible to age-associated alterations in methylation levels of rDNA promoter regions, suggesting that sperm rDNA promoter methylation levels can be applied to DNA methylation-based age prediction, and that the aberrant methylation of rDNA promoters may be partially responsible for enhanced disease susceptibility of offspring sired by older fathers. Methylation levels of sperm rDNA promoter regions may correlate with polypronuclei rates of IVF programs. [ABSTRACT FROM AUTHOR]

Objective: To analyze the concentration of growth factors secreted by autologous cumulus cell clusters during in vitro human embryo co-culture and investigate the impact of culture supplementation with autologous cumulus cell clusters on embryo development and pregnancy rate as compared to standard culture procedure. Design: Randomized prospective comparative study. Setting: Private IVF clinic. Patients: 90 IVF patient couples ranging at the age between 35 and 40 (mean age of 36.5) agreed to participate in this study. In this IVF group, 64 first trials, 22 s trials and 4 third trials were included. 48 cases have been terminated at day 3 of culture and 42 of them have been continued up to day 5. Of the 48 cases assigned for day-3 culture, 208 MII-oocytes were randomly assigned for co-culture and 197 MII-oocytes were assigned for standard culture. The selection was done by alternating the oocyte immediately after stripping to co-culture or control, starting always with co-culture. Interventions: All samples were analyzed with Milliplex factor-specific magnetic-bead panels with phycoerythrin fluorescent factor-specific antibodies using immunofluorescence cytometry technology by Lab Supplies Inc. laboratories in Athens, Greece. The MFI (Mean Fluorescence Intensity) values were calibrated and the readings were translated in pg/ml and calculated against the background values of culture medium alone. The statistical analysis of all data were processed with the Two-tailed T-test form. Main outcome measures: 36 IVF cases terminated at day 3 were randomly chosen. Supernatants from 17 cases were analyzed for seven different growth factors, namely, epidermal growth factor (EGF), fibroblast growth factor 1 and 2 (FGF-1 and FGF-2), vascular endothelial growth factor A, C and D (VEGF-A, VEGF-C and VEGF-D) and Leptin. Supernatants from 19 cases were analyzed for Insulin-like Growth Factor I and II (IGF-I and IGF-II). Results: VEGF-A and VEGF-C were found at statistically significant levels (p

Introduction: Insulin like growth factor-1 (IGF-1) has been found to stimulate follicular development, estrogen and progesterone production and oocyte maturation. This study aims to detect the changes in the follicular fluid IGF-1 levels in normo-ovulatory women undergoing in vitro fertilization (IVF) cycle and evaluate the possibility of IGF-1 to be a predictive marker for IVF outcome in normo-ovulatory women. Materials and methods: This prospective cross-sectional study was performed among 88 IVF normo-ovulatory women who were categorized according to IVF pregnancy outcome (clinical pregnancy) into two groups: 55 pregnant women and 33 non-pregnant women. Follicular fluid IGF-1 levels have been measured at the time of oocyte retrieval by utilizing enzyme linked immune-sorbent assay (IGF-1 ELISA kit, Diametra, Inc, Italy). The relationship between follicular fluid IGF-1 (FF IGF-1) levels and the number of oocytes retrieved, number of mature oocytes, number of embryos, fertilization and clinical pregnancy rate were assessed. The demographic data were similar between two groups as regards age and BMI. Results: FF IGF-1 levels were significantly higher in pregnant women than in non-pregnant women (90.11 ± 44.31 ng/ml, 69.07 ± 30.55 ng/ml) respectively (p

Background: Our aim was to study the effect of GnRH agonist and antagonist protocols of ovarian stimulation on oxidative stress parameters in serum and the influence of oxidative stress parameters change on the outcome of IVF cycles. Methods: This prospective study included 82 patients who underwent IVF procedures. We determined SOD, MDA and SH groups in serum. Serum samples were obtained between the second and fourth day of the cycle and on the day of HCG administration during ovarian stimulation. Results: Patients were divided into two groups depending on the protocol of stimulation. The mean total and mature oocytes number and number of fertilized oocytes were higher in GnRH agonist group. There was no significant difference in biochemical pregnancy, miscarriage and live -birth rate in both groups. Mean serum SOD was significantly lower, while mean serum MDA and SH groups were significantly higher after ovarian stimulation. Delivery rate was higher in patients without OS while miscarriage rate was higher in patients with OS. Conclusions: Our study confirmed that there is a difference in the concentration of oxidative stress parameters before and after ovarian stimulation. IVF outcome is better in patients without OS after ovarian stimulation. However, the protocol of ovarian stimulation is neither associated with a change in oxidative stress parameters nor with the outcome of ART procedures.

Background: Elective freezing of all embryos, followed by frozen-thawed ET cycles emerged to prevent risk of Ovarian Hyperstimulation Syndrome and to allow endometrium recovery after Controlled Ovarian Stimulation, leading to better IVF outcomes. Blastocyst Freeze-all policy can minimize the number of abnormal embryos and consequently failed ETs, but its efficacy in terms of cumulative rates has not been studied yet.Methods: A prospective cohort observational study was carried out in Assisting Nature, Center of Assisted Reproduction and Genetics, in Thessaloniki, Greece from January 2014 until December 2017. 244 patients- normal or high responders- underwent COS with recFSH and Freeze-all policy with blastocyst culture. The included patients were 18-39 years and achieved clinical pregnancy and/or live birth or had all their vitrified blastocysts transferred in subsequent frozen-thawed cycles. Women were divided into four groups (group A: 1–2 blastocysts frozen; group B: 3–4; group C: 5–6; group D ≥7 blastocysts frozen) or seven groups (group I: 1–2 blastocysts frozen, group II: 3, group III: 4, group IV: 5, group V: 6, group VI: 7; group VII: ≥8 blastocysts frozen), according to the numerical range or to the absolute number of vitrified blastocysts, respectively.Results: The main outcome of the study was the CLBR achieved by frozen-thawed ETs, according to the number of the vitrified blastocysts. Higher CLBR are expected, when at least 3 blastocysts are formed (group B: 65.2%) and at least 2 frozen-thawed ETs are performed, reaching highest rates (88%) by group D (≥7 vitrified blastocysts). Similarly, CLBR is significantly increasing with the absolute number of the vitrified blastocysts, ranging from 20%, when 1–2 blastocysts are vitrified (group I) to 82.4% when ≥8 blastocysts are available.Conclusions: A higher number of vitrified blastocysts is associated with higher CLBR in women

Objective: To investigate the effects of β-cell dysfunction on IVF outcomes in women with PCOS., Methods: This retrospective cohort study includes 1,212 women with PCOS undergoing their first IVF cycle between September 2010 and December 2019. Beta-cell dysfunction was measured by homeostasis model assessment of β-cell function (HOMA-β) index., Results: In quartiles of HOMA-β, the incidence of miscarriage dramatically increased from 10.2% (Q1) to 31.1% (Q4) ( P for trend <0.001). Likewise, the incidence of miscarriage in quartiles of HOMA-β also showed a similar trend ( P for trend <0.001). After adjusting for confounding factors, logistic regression analyses showed that high HOMA-IR values were independently associated with a high risk of miscarriage, with the odds ratios (OR) and 95% confidence intervals for quartiles 2-4 versus quartile 1 were 1.30 (0.69-2.46), 1.82 (0.97-3.43), and 3.57 (1.86-6.85), respectively ( P for trend <0.001). When analyzed jointly, women in the highest HOMA-IR and highest HOMA-β group exhibited the highest risk for miscarriage compared with all other groups. Furthermore, higher HOMA-IR values were associated with higher risks of miscarriage among PCOS women regardless of HOMA-β values., Conclusions: β-cell dysfunction is independently associated with increased miscarriage rate and decreased live birth rate in women with PCOS. It also plays a synergistic role with IR in terms of the reproductive outcomes, while the influence of IR overweighs that of β-cell dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewers YH and JZ shared parent affiliation with the AUTs CL, YL, HZ, HY to the handling editor at time of review., (Copyright © 2024 Huang, Liu, Ding, Li, Zhou, Wang and Yang.)