IVF/intracytoplasmic Sperm Injection Research Articles

Comparison of embryo quality and pregnancy outcomes for patients with low ovarian reserve in natural cycles and mildly stimulated cycles: a cohort study

Background As women with low ovarian reserve embark on the challenging journey of in-vitro fertilisation (IVF) treatment, the choice between natural and mildly stimulated cycles becomes a pivotal consideration. It is unclear which of these two regimens is superior for women with low ovarian reserve. Our study aims to assess the impact of natural cycles on embryo quality and pregnancy outcomes in women with low ovarian reserve undergoing IVF treatment compared to mildly stimulated cycles. Methods This retrospective study enrolled consecutive patients with low ovarian reserve who underwent IVF/intracytoplasmic sperm injection (ICSI) at Guangdong Second Provincial General Hospital between January 2017 and April 2021. The primary outcome for pregnancy rate of 478 natural cycles and 448 mild stimulated cycles was compared. Secondary outcomes included embryo quality and oocyte retrieval time of natural cycles. Results The pregnancy rate in the natural cycle group was significantly higher than that in the mildly stimulated cycle group (51.8% vs. 40.1%, p = 0.046). Moreover, natural cycles exhibited higher rates of available embryos (84.1% vs. 78.6%, p = 0.040), high-quality embryos (61.8% vs. 53.2%, p = 0.008), and utilisation of oocytes (73% vs. 65%, p = 0.001) compared to mildly stimulated cycles. Oocyte retrievals in natural cycles were predominantly performed between 7:00 and 19:00, with 94.9% occurring during this time frame. In natural cycles with high-quality embryos, 96.4% of oocyte retrievals were also conducted between 7:00 and 19:00. Conclusion Natural cycles with appropriately timed oocyte retrieval may present a valuable option for patients with low ovarian reserve.

Nonlinear relationship between gonadotropin total dose applied and live birth rates in non-PCOS patients: a retrospective cohort study

The purpose of this article is to explore the relationship between the total dose of follicle-stimulating hormone (FSH) applied during controlled ovulation stimulation and the live birth rates (LBRs) in non-PCOS population. Many studies have found no difference between the dose of FSH application and pregnancy outcomes such as clinical pregnancy rates after fresh embryo transfer. However, a recent large retrospective analysis found a negative correlation between live birth rates and increasing dose of FSH. It is still controversial about the association between FSH dose and LBRs. In addition, no studies have yet explored the nonlinear relationship between FSH and LBRs. This cohort study included a total of 11,645 patients who had accepted IVF/intracytoplasmic sperm injection (ICSI) at the second hospital of Hebei medical university between December 2014 to December 2019. PCOS was identified by Rotterdam PCOS criteria. We researched the association between FSH total dose and live birth rates (LBRs) using multivariate regression analysis. In addition, a model for nonlinear relationships based on a two-part linear regression was applied. The analysis of threshold effects indicated that LBR increased with every 1000 IU FSH when the concentration of FSH was lower than 1410 IU (OR 1.55, 95% CI [1.05, 2.28]); however, a negative association between FSH dose and LBR (OR 0.94, 95% CI [0.89, 0.99]) was found when the FSH total dose was higher than 1410 IU. It is worth noting that the relationship between LBR and FSH dose varied among patients of different ages (OR 0.92 vs 1.06, P for interaction < 0.05).

Efficacy and safety of recombinant human granulocyte colony-stimulating factor in patients with poor ovarian response: protocol for a multicentre, randomised, controlled trial

IntroductionApproximately 17.5% of couples of reproductive age have experienced infertility. Women with a poor ovarian response (POR) must undergo in vitro fertilisation (IVF) and embryo transfer to achieve pregnancy. However,...

The association between serum prolactin levels and live birth rates in non-PCOS patients: A retrospective cohort study.

This paper aimed to analyze the relationship between baseline prolactin (PRL) levels and live birth rates (LBRs) in patients undergoing embryo transfer who did not have polycystic ovarian syndrome (PCOS) using a retrospective design. Patient(s): A total of 20,877 patients who had undergone IVF/intracytoplasmic sperm injection (ICSI) between December 2014 and December 2019. We examined the association between PRL concentrations and LBRs using multivariate regression analysis. In addition, a model for nonlinear relationships based on a two-part linear regression was developed. Following adjustment for confounding factors, multivariate regression analysis confirmed a statistically significant correlation between serum PRL and LBR. Particularly, when blood PRL content was less than 14.8 ng/mL, there exists a positive relation between serum PRL and LBRs. In contrast, once PRL concentrations surpassed the inflection point at 14.8 ng/mL, a meaningful relationship could no longer be inferred between serum PRL and LBR. Basal serum PRL levels were segmentally connected with LBRs.

Local production of 17β-oestradiol in the endometrium during the implantation window: a pilot study.

Sex steroids are converted to bioactive metabolites and vice versa by endometrial steroid-metabolising enzymes. Studies indicate that alterations in this metabolism might affect endometrial receptivity. This pilot study determined whether the endometrial formation and inactivation of 17β-oestradiol differed between the supposedly embryo-receptive endometrium and non-receptive endometrium of women undergoing IVF/intracytoplasmic sperm injection (ICSI). Endometrial biopsies were obtained from IVF/ICSI patients 5-8 days after ovulation in a natural cycle, prior to their second IVF/ICSI cycle with fresh embryo transfer (ET). Endometrial biopsies from patients who achieved clinical pregnancy after fresh ET (n = 15) were compared with endometrial biopsies from patients that did not conceive after fresh ET (n = 15). Formation of 17β-oestradiol (oxidative 17β-hydroxysteroid dehydrogenases (HSDs)), oestrone (reductive HSD17Bs) and inhibition of HSD17B1 activity were determined by high-performance liquid chromatography. The endometrial transcriptome was profiled using RNA sequencing followed by principal component analysis and differentially expressed gene analysis. The false discovery rate-adjusted P < 0.05 and log fold change >0.5 were selected as the screening threshold. Formation and inactivation of 17β-oestradiol resulted similar between groups. Inhibition of HSD17B1 activity was significantly higher in the non-pregnant group when only primary infertile women (n = 12) were considered (27.1%, n = 5 vs 16.2%, n = 7, P = 0.04). Gene expression analysis confirmed the presence of HSD17B1 (encoding HSD17B1), HSD17B2 (encoding HSD17B2) and 33 of 46 analysed steroid metabolising enzymes in the endometrium. In the primary infertile subgroup (n = 10) 12 DEGs were found including LINC02349 which has been linked to implantation. However, the exact relationship between steroid-metabolising enzyme activity, expression and implantation outcome requires further investigation in larger, well-defined patient groups. Sex hormones are produced and broken down by enzymes that can be found in the endometrium (the inner lining of the womb). This enzyme activity might influence the chances of becoming pregnant. We compared (i) enzyme activity in the endometrium of 15 women who did and 15 women who did not become pregnant in their second in vitro fertilisation attempt, (ii) how enzyme activity can be blocked by an inhibitor, and (iii) differences in gene expression (the process by which instructions in our DNA are converted into a product). Enzyme activity was similar between groups. We found that in women who have never been pregnant in the past, inhibition of enzyme activity was higher and found differences in a gene that has been linked to the implantation of the embryo, but future studies should be performed in larger, well-defined patient groups to confirm these findings.

Oocyte-derived growth differentiation factor 9 suppresses the expression of CYP17A1 and androgen production in human theca cells

ObjectiveTo investigate the direct effect of growth differentiation factor 9 (GDF9) on androgen production in human theca cells. DesignExperimental study SettingTertiary hospital-based research laboratory Patient(s)Women underwent IVF/intracytoplasmic sperm injection (ICSI) at our clinic were included in this study. Intervention(s)Primary cultured human theca cells from women undergoing IVF/ICSI treatment were treated with GDF9, Activin receptor-like kinase 5 (ALK5) inhibitor, and SMAD4 agonist. Main Outcome Measure(s)The expression of androgen synthesis-related gene StAR, CYP17A1, and LHCGR, levels of androstenedione and testosterone, phosphorylation of SMAD2/3 and the interaction between bone morphogenetic protein receptor II (BMPRII) and ALK5 were evaluated by RT-qPCR, Western blot, enzyme-linked immunosorbent assays, and co-immunoprecipitation assays respectively. ResultsGDF9 decreased StAR, CYP17A1, and LHCGR expression levels in human theca cells, which was prevented by the treatment with the ALK5 inhibitor, and suppressed production of androgen in human theca cells. GDF9 increased SMAD2/3 phosphorylation, and the ALK5 inhibitor also suppressed this effect. BMPRII and ALK5 bound to each other following GDF9 stimulation. The SMAD4 agonist kartogenin also decreased mRNA levels of StAR and CYP17A1, and protein levels of StAR in human theca cells. ConclusionGDF9 can activate the BMPRII-ALK5-SMAD2/3 signaling pathway, suppress CYP17A1 expression and androgen production in human theca cells.

Fertility and Obstetric Outcomes of Assisted Reproductive Technology (ART) in Women With Adenomyosis Following Gonadotropin-Releasing Hormone Agonist Therapy: A Single-Center Experience.

Adenomyosis is an ambiguous disorder causing a wide variety of implications from dysmenorrhea, heavy menstrual bleeding, and infertility to pregnancy complications. Adenomyosis is associated with altered endocrine and inflammatory milieu, resulting in impaired implantation and reduced fertility potential. It is also associated with increased incidence of obstetric complications such as miscarriage, antepartum hemorrhage, placental mal-position, hypertensive disorders, small for gestational age-intrauterine growth restriction (SGA-IUGR), cesarean section, preterm labor, preterm premature rupture of membranes (PPROM), and neonatal intensive care unit (NICU) admissions. The aim of our study was to investigate the fertility and obstetric outcomes in women with adenomyosis treated with GnRH agonists compared to controls with normal uteri undergoing in-vitro fertilization (IVF) at our center, thereby establishing the role of gonadotropin-releasing hormone (GnRH) agonists in managing sub-fertile women with adenomyosis. We carried out a retrospective cohort study at our hospital to analyze the effects of adenomyosis on IVF and pregnancy outcomes. This study (n=83) involves women with adenomyosis between the ages of 21 and 37 years who were followed up at our center between 2013 and 2022. The controls (n=83) were selected from women who underwent IVF-intracytoplasmic sperm injection (IVF-ICSI) for tubal or mild male factor infertility with normal appearing uterus within the same time frame. Women with adenomyosis were given GnRH agonist as long/ultralong agonist protocol before controlled ovarian stimulation or as down-regulated frozen embryo transfer (FET). The length of suppression was between one and six months based on the size of the uterus and response to treatment. Fertility and obstetric outcomes were analyzed. The implantation rates were found to be equivocal: 54.2% and 53% in the adenomyosis and control groups, respectively (p=0.208). The cumulative live birth rate was 50.6% and 48.2% in the study and control groups,respectively (p=0.341). The biochemical pregnancy rate and the first- and second-trimester miscarriage rates were not significantly different between the group with adenomyosis and the group with normal uterus. The incidence of preterm deliveries and antepartum hemorrhage was found to be significantly increased in the study group. Medical management in women with adenomyosis optimizes the live birth rates giving results at par with the control population.

Impact of Homocysteine as a Preconceptional Screening Factor for In Vitro Fertilization and Prevention of Miscarriage with Folic Acid Supplementation Following Frozen-Thawed Embryo Transfer: A Hospital-Based Retrospective Cohort Study.

Homocysteine is an amino acid naturally produced in the body and metabolized via the methionine cycle. High homocysteine levels can increase the risk of infertility and pregnancy complications, such as preeclampsia, preterm delivery, miscarriage, and low birth weight. Preconceptional homocysteine levels may be reduced by taking folic acid supplements to reduce the risk of such complications. This cross-sectional, hospital-based study was conducted to examine the role of homocysteine in 1060 infertile women with a history of IVF/intracytoplasmic sperm injection (ICSI) failure. We analyzed whether folic acid intervention altered homocysteine levels and influenced reproductive outcome. We found that a higher homocysteine level was statistically associated with a lower fertilization rate in patients with a history of IVF/ICSI failure. There was an inverse relationship between homocysteine levels and serum 25(OH)VD, and a trend towards lower anti mullerian hormone in the group with higher homocysteine levels. This is the first interventional study to identify that folic acid supplementation improved pregnancy outcomes following freeze embryo transfer (FET) in women with a history of FET failure by monitoring the reduction in homocysteine levels. Therefore, folic acid supplementation and homocysteine level monitoring may constitute a novel intervention for improving IVF/ICSI pregnancy outcomes.

A Proteomic Analysis of Human Follicular Fluid: Proteomic Profile Associated with Embryo Quality.

Embryo selection is a key point of in vitro fertilization (IVF). The most commonly used method for embryo selection is morphological assessment. However, it is sometimes inaccurate. Follicular fluid (FF) contains a complex mixture of proteins that are essential for follicle development and oocyte maturation. Analyzing human FF proteomic profiles and identifying predictive biomarkers might be helpful for evaluating embryo quality. A total of 22 human FF samples were collected from 19 infertile women who underwent IVF/intracytoplasmic sperm injection (ICSI) treatment between October 2021 and November 2021. FFs were grouped into two categories on the basis of the day 3 embryo quality, grade I or II in the hqFF group and grade III in the nhqFF group. FF was analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The key differentially expressed proteins (DEPs) were validated by parallel reaction monitoring (PRM) and enzyme-linked immunosorbent assay (ELISA). Differentially expressed proteins were further analyzed using DAVID software. A total of 558 proteins were identified, of which 50 proteins were differentially expressed in the hqFF versus nhqFF group, including 32 upregulated proteins (> 1.20-fold, P < 0.05) and 18 downregulated proteins (< 0.67-fold, P < 0.05). Bioinformatics analyses showed that the upregulated DEPs were enriched in components of the coagulation and complement systems and negative regulation of peptidase activity, while the downregulated DEPs were enriched in molecular function of extracellular matrix structural and constituent collagen binding. Our results suggested that a number of protein biomarkers in FF were associated with embryo quality. It may help develop an effective and noninvasive method for embryo selection.

P-780 Oocyte proteome and cumulus cell transcriptome analysis reveal oocytes live in a hypoxic microenvironment underlie the arrest of human early embryos in vitro culture

Abstract Study question Can cumulus cell transcriptome analysis combined with oocyte single-cell proteomics uncover the cause of human early embryos arrest during assisted reproductive treatment? Summary answer Oocytes living in a hypoxic microenvironment underlie the arrest of human early embryos at cleavage stage in vitro culture. What is known already Preimplantation embryo developmental potential largely depends on gamete quality in assisted reproduction treatment. Human embryonic genome major activation has occurred by the eight-cell stage, up to 3 days after fertilization. Therefore, to a large extent, the development competence of embryo at cleavage stage relies on oocytes quality, which acquire during follicle development. Cumulus cell (CC) plays an essential role in transmitting signals within the ovary and supporting oocyte growth and maturation. We used whole transcriptome analysis of cumulus cells (CC) and single-cell proteomics of oocyte to gain insights into the molecular mechanisms of embryo development arrest at cleavage stage. Study design, size, duration Fifty CCs samples and eleven oocyte samples were obtained from fifty-eight couples who underwent IVF/intracytoplasmic sperm injection (ICSI) treatment. The total CCs average age was 30.18±4.51(control group) and 32.59±3.43 (DA group). The total oocyte average age was 33.13±4.83. Donated CCs were recruited between January 2018 and December 2019. Donated oocytes were recruited between September 2022 and October 2022. Participants/materials, setting, methods CCs samples were obtained from 33 patients whose rate of good-quality embryos is above 90% (as control) and 17 patients with more than 90% embryos fail to reach six-cell stage (Grade II) on day 3 (as development arrest, DA). Oocytes at GV and MI stage respectively were collected for proteomics. Differentially expressed genes were analyzed using the R package DESeq2 or DEP (filtered with q-value≤0.05 and Foldchange≥1.5). EGSEA package was used to perform pathway analysis. Main results and the role of chance RNA sequencing identified 18458 genes expressed in CCs of both groups, 31 of which were differentially expressed. CCs from patients whose embryos development arrested, contains 36 differentially expressed genes (DEGs) up-regulated and 4 DEGs down regulated. Gene ontology showed that up-regulated genes were significantly enriched with annotations related to oxidoreductase activity, mitochondrial respiratory chain complex IV and response to hypoxia. TF enrichment analysis found out that up-regulated DEGs was enriched in hypoxia-inducible factor 1 (HIF-1) induced transcription. It has been reported that HIF-1-mediated gene expression can be elicited by hypoxia, which could restrict mitochondrial biogenesis and ATP-dependent cellular processes. So, we supposed that oocytes live in an ultra-hypoxic microenvironment underlie human early embryos arrest. In consideration of the difficulty in detection of the oxygen level in antral follicles cavity, the protein level changes of oocytes in DA group were used to reflect oocyte status. There were 47 proteins up-regulated and 105 proteins down-regulated at GV stage; 55 gene up-regulated and 48 genes down-regulated at MI stage. Among these, overlap with up-regulated genes in both stages included tuberous sclerosis complex1(TSC1) and Neutral amino acid transporter A (ASCT1), which play key roles in cellular response to oxygen-glucose and hypoxia stress response. Limitations, reasons for caution Because of the lack of credible data reflecting accurately the dissolved O2 concentration adjacent to an oocyte. Determination of dissolved O2 within antral follicles is fraught with technical difficulties. We can just verify our hypothesis by single-cell proteomics of oocyte and Ultra-Low-oxygen treatment in vitro. Wider implications of the findings We provide a new hypothesis that hypoxic follicular harmed oocyte quality, causing human early embryos arrest. The DEGs we detected in CCs and oocyte could be the biomarker candidates for embryo developmental potential. Ovarian stimulation protocols for embryo development arrested patients could consider diminishing oocyte exposure time in hypoxic follicles. Trial registration number Not applicable

Prevalence of Vitamin D Insufficiency and Its Determinants among Women Undergoing In Vitro Fertilization Treatment for Infertility in Sweden.

There is a lack of research on women with infertility in the northern latitudes, where vitamin D insufficiency is high. Therefore, this study aimed to assess the prevalence and determinants of vitamin D insufficiency (serum 25(OH)D concentration < 50 nmol/L) among women undergoing in vitro fertilization (IVF) treatment. Thus, 265 women scheduled for IVF/intracytoplasmic sperm injection (ICSI) between September 2020 and August 2021 at Sahlgrenska University Hospital in Gothenburg, Sweden, were included. Data on serum 25(OH)D concentration, vitamin D intake, and sun exposure were collected via questionnaires and blood samples. Approximately 27% of the women had 25(OH)D insufficiency, which was associated with longer infertility duration. The likelihood of insufficiency was higher among women from non-Nordic European countries (OR 2.92, 95% CI 1.03-8.26, adjusted p = 0.043), the Middle East (OR 9.90, 95% CI 3.32-29.41, adjusted p < 0.001), and Asia (OR 5.49, 95% CI 1.30-23.25, adjusted p = 0.020) than among women from Nordic countries. Women who did not use vitamin D supplements were more likely to have insufficiency compared with supplement users (OR 3.32, 95% CI 1.55-7.10, adjusted p = 0.002), and those who avoided sun exposure had higher odds of insufficiency compared to those who stayed "in the sun all the time" (OR 3.24, 95% CI 1.22-8.62, adjusted p = 0.018). Women with infertility in northern latitudes and those from non-Nordic countries who avoid sun exposure and do not take vitamin supplements have a higher prevalence of 25(OH)D insufficiency and longer infertility duration.

Oocyte donation outcomes in endometriosis patients with multiple IVF failures

What are the reproductive outcomes and the prognostic factors of live birth rates in patients with endometriosis referred to oocyte donation after multiple IVF failures? Observational cohort study including all women with endometriosis-related infertility and two or more failed IVF/intracytoplasmic sperm injection (ICSI) cycles referred to oocyte donation between January 2013 and June 2022. Endometriosis was diagnosed based on published imaging criteria, and was confirmed histologically in women who had a history of surgery for endometriosis. The main outcome measured was the cumulative live birth rate (CLBR). The characteristics of women who had a live birth were compared with those who did not using univariate and multivariate analysis to identify determinant factors of fertility outcome. Fifty-seven patients underwent 90 oocyte donation cycles after 244 failed autologous IVF cycles. The mean ± SD age of the population was 36.8 ± 3.3 years, with a mean duration of infertility of 3.6 ± 2.2 years, and a mean number of autologous IVF/ICSI cycles of 4.4 ± 2.3 cycles per patient. Three patients (5.3%) had superficial peritoneal endometriosis, two patients (3.5%) had ovarian endometriomas, and 52 patients (91.2%) had deep infiltrating endometriosis, among which 30 patients (57.7%) had bowel lesions. Thirty patients (52.6%) had associated adenomyosis. Overall, CLBR per patient was 36/57 (63.2%). After multivariate analysis, only being nulligravida (P=0.002) remained an independent negative predictive factor of the live birth rate. Previous surgery did not impact reproductive outcomes. This study suggests that oocyte donation appears to be a viable option to optimize the live birth rate in women with endometriosis-related infertility and recurrent IVF failures.

Impact of thyroid autoimmunity on pregnancy outcomes in euthyroid patients with recurrent implantation failure

Research questionDoes thyroid autoimmunity (TAI) adversely affect pregnancy outcomes after IVF/intracytoplasmic sperm injection (ICSI) in euthyroid patients with recurrent implantation failure (RIF)? DesignThis retrospective cohort study was conducted at the Reproductive Hospital Affiliated with Shandong University from November 2016 to September 2021. A total of 1031 euthyroid patients diagnosed with RIF were enrolled. Based on serum thyroid autoantibody concentrations, the participants were divided into two groups: the TAI-positive group (219 women with RIF) and the TAI-negative group (812 women with RIF). The parameters were compared between the two groups. Additionally, logistic regression was used to adjust related confounders for primary outcomes, and subgroup and stratified analyses were performed according to different thyroid autoantibody types and TSH concentrations. ResultsThere was no significant difference in ovarian reserve, ovarian response, embryo quality, pregnancy outcome or neonatal outcome between the two groups (P > 0.05). After adjustments for age, body mass index, thyroid-stimulating hormone and free thyroxine, the biochemical pregnancy rate in the TAI-positive group was significantly lower than that in the TAI-negative group (odds ratio 1.394, 95% CI 1.023–1.901, adjusted P = 0.036). Regarding the implantation rate, clinical pregnancy rate, pregnancy loss rate, stillbirth rate and live birth rate, no significant differences were observed even with subgroup and stratified analyses (P > 0.05). ConclusionsTAI had no impact on pregnancy outcomes in euthyroid RIF patients who underwent IVF/ICSI. In clinical practice, interventions targeting thyroid autoantibodies in these patients should be implemented with caution and additional evidence is needed.

The impact of semen parameters on ICSI and pregnancy outcomes in egg recipient cycles with PGT-A.

The egg donation model offers an opportunity to isolate the male factor and evaluate its impact on IVF-intracytoplasmic sperm injection and pregnancy outcomes. To study the effect of non-obstructive azoospermia on intracytoplasmic sperm injection and pregnancy outcomes compared with severe oligozoospermia and mild-to-moderate oligozoospermia in egg recipient cycles. This is a retrospective longitudinal cohort study, including 1594 patients who underwent intracytoplasmic sperm injection in egg recipient cycles with preimplantation genetic testing for aneuploidies. The cohort was divided into three groups: couples with non-obstructive azoospermia accounting for 479 patients (30%); couples with severe oligozoospermia (sperm number <5×106 /mL), accounting for 442 patients (27.8%); couples with mild-to-moderate oligozoospermia, with sperm number >5×106 and <15×106 /mL, accounting for 673 patients (42.2%). The fertilisation rate was significantly reduced in the non-obstructive azoospermia group as compared with the severe oligozoospermia and the mild-to-moderate oligozoospermia group: 30.3% versus 63% and 77.3% (p<0.05). Logistic regression analysis adjusted for confounders highlighted non-obstructive azoospermia as a negative predictor of obtaining a euploid blastocyst both per injected oocyte and per obtained blastocyst. The miscarriage rate in the non-obstructive azoospermia group was 11.8%; higher than the severe oligozoospermia and mild-to-moderate oligozoospermia groups (7% and 2.7%) (p<0.05). The live birth rate per embryo transfer (ET) was significantly lower in the non-obstructive azoospermia group compared with the severe oligozoospermia and the mild-to-moderate oligozoospermia group (20.4% vs. 30.3% and 35.4%, p<0.05). The risk of preterm labour was significantly higher in the non-obstructive azoospermia group, compared with the severe oligozoospermia and mild-to-moderate oligozoospermia group (55.1% vs. 46.8% and 16.1%, p<0.001), and this difference was observed in both singleton and twin pregnancies. In our retrospective comparative study, non-obstructive azoospermia significantly affects early embryonic potential and live birth rates per cycle and per embryo transfer. It is also associated with higher risk of preterm birth. Future prospective multi-centre studies are needed to highlight the effect of sperm quality on ART and pregnancy outcomes.

Correlation analysis of sperm DNA fragmentation index with semen parameters and the effect of sperm DFI on outcomes of ART

Routine semen analysis provides limited information about a man’s male reproductive potential and can not always fully explain male infertility. Many male infertilities are caused by sperm DNA defects that routine semen quality analyses fail to detect. In this study, we analyzed the association of sperm DNA fragmentation index (DFI) with the semen routine, sperm morphology, in vitro fertilization embryo transfer (IVF-ET)/intracytoplasmic sperm injection (ICSI). Further, we explored the predictive value of sperm DFI in evaluating male fertility and the outcome of IVF-ET/ICSI. Data on sperm DFI, sperm routine, and sperm morphology were collected from 1462 males with infertility. According to DFI levels, there were 468 cases in group I (DFI ≤ 15%), 518 cases in group II (15% < DFI < 30%), and 476 cases in group III (DFI ≥ 30%). The correlations of sperm DFI with semen routine and malformation rate were analyzed. Seminal plasma malondialdehyde (MDA), and total antioxidant capacity (TAC) were assessed. Sperm DFI, semen routine, and sperm morphology were detected in male patients of 101 pairs of IVF-ET/ICSI infertile couples and subdivided into IVF-I group (DFI ≤ 15%), IVF-II group (15% < DFI < 30%), IVF-III group (DFI ≥ 30%), ICSI-I group (DFI ≤ 15%), ICSI-II group (15% < DFI < 30%) and ICSI-III group (DFI ≥ 30%) according to DFI value. The effect of sperm DFI on the outcome of IVF-ET/ICSI was analyzed. There were significant differences in sperm survival rate, sperm concentration, and PR% between groupIII and group II (P < 0.01). There were significant differences in sperm survival rate, sperm concentration and PR% between group III and group I (P < 0.01). There was no significant difference in semen volume, age, abstinence days, or percentage of normal sperm between the three groups (P > 0.05). DFI was positively correlated with MDA content ( P < 0.01) and negatively correlated with TAC (P < 0.01). Sperm DFI was negatively correlated with sperm survival rate, sperm concentration, and PR% (P < 0.01). There was no correlation with age, abstinence days, semen volume, or percentage of normal-form sperm (r = 0.16, 0.05, 0.04, -0.18, p > 0.05). Compared with IVF-I group, the sperm concentration and PR were decreased in IVF-III group. The sperm malformation rate was higher in IVF-III group than that in IVF-II group. Comparatively, the PR was decreased in ICSI-III group. The sperm malformation rate was higher in ICSI-III group than that of the ICSI-I group (P < 0.05). There were no statistically significant differences in fertilization rate, cleavage rate, embryo rate, and clinical pregnancy rate between IVF group or ICSI group, and between all subgroups (P > 0.05). Sperm DFI is negatively associated with sperm survival rate, sperm concentration, and PR%. Antioxidants can decrease the rate of DNA fragmentation. Sperm DFI has proven to be very valuable in the male fertility evaluation, but its significance as a predictor of pregnancy outcomes following assisted reproductive technology. (ART) requires further investigation.

Effect modification by developmental stage of embryos on the association between late follicular phase progesterone elevation and live birth in fresh transfers

BackgroundLate follicular phase progesterone elevation (LFPE) during ovarian stimulation is associated with reduced live birth rates (LBRs) after cleavage-stage embryo transfer. However, due to better synchronization with a stimulated endometrium, prior studies shown that LFPE had no effect on transferring embryos at blastocyst stage. The study aim to exam whether the developmental stage of embryos and serum progesterone levels on the day of human chorionic gonadotropin (hCG) administration jointly affect the odds of live birth in fresh fresh IVF/intracytoplasmic sperm injection (ICSI) cycles. MethodsThe single-center retrospective cohort study included a total of 4,471 fresh embryo transfer cycles with 2,342 at cleavage stage versus 2,129 at blastocyst stage. Patients underwent IVF/ICSI with ovarian stimulation in gonadotropin-releasing hormone antagonist protocol. The serum progesterone level was examined both as a continuous variable and as a categorical variable by quartiles. Analysis was performed using the generalized estimating equations framework and multivariate regression models.ResultsLBRs were inversely associated with progesterone as a continuous variable on the day of hCG in both the cleavage-stage (crude OR 0.87, 95%CI 0.73–1.03; adjusted OR 0.80, 95% CI 0.65–0.98) and the blastocyst-stage (crude OR 0.66, 95%CI 0.56–0,78; adjusted OR 0.61, 95%CI 0.50–0.73) groups. The interaction testing was highly significant (P = 0.018) indicating an effect modifying role of stage of embryos transferred on the association of pregesterone values with the LBRs in fresh cycles. A similar pattern for a greater reduction in ORs for live birth in cycles with blastocysts transfer was also observed when progesterone was analyzed by interquartile ranges. The findings remained unchanged in subgroup analysis stratified by types of ovarian response.ConclusionsIn fresh cycles, detrimental effect of late follicular phase progesterone elevation on live birth was more prominent in blastocyst-stage group compared with that in clevaged-stage group.

Evaluation of Fertility Success Rate with Simultaneous Transfer of Embryos with Different Qualities in IVF/ICSI Candidates

Background: One of the most important factors in the success of assisted reproductive techniques is the quality of the embryo generated in the laboratory. Whether to transfer only one high-quality embryo or a combination of high- and low-quality embryos is a dilemma. Objectives: The present study reviewed the embryo transfer records of IVF/intra cytoplasmic sperm injection (ICSI) patients in Dezful Infertility Center, Iran, to evaluate the impact of the simultaneous transfer of a low-quality embryo on the growth and implantation of a high-quality embryo and live birth. Methods: This cross-sectional study evaluated the files and records of 802 patients undergoing IVF/ICSI at Dezful Infertility Treatment Center from 2013 to September 2020. The patients were classified into group 1: Patients with the transfer of only one grade A (equal blastomeres without fragmentation) embryo, group 2: Patients with the transfer of two grade A and B (equal blastomeres with slight fragmentation) embryos, group 3: Patients with the transfer of two grade A and C (unequal blastomeres with or without fragmentation) embryos, and group 4: Patients with the transfer of two grade C and B embryos. Results: The mean age of women and men was 32.52 ± 5.10 and 37.59 ± 6.60 years, respectively. Age, duration of infertility, cause of infertility, endometrial diameter, estradiol level, oocyte number, and embryo number had no significant differences between the groups (P &gt; 0.05). Also, the findings indicated no significant differences between the groups in terms of implantation rate, live birth rate, fertility rate, multiple pregnancies rate, and chemical and clinical abortions (P &gt; 0.05). Conclusions: It seems that the simultaneous transfer of embryos with different qualities does not affect the success rate and fertility outcomes in IVF/ICSI candidates.

COVID-19 infection and vaccine have no impact on in-vitro fertilization (IVF) outcome

To investigate the effect of COVID-19 infection or vaccine on IVF outcome. This is a multicenter retrospective study. Data were collected from all patients treated in the ART units between September and November 2021 after the vaccination of the general population began. Medical records of all patients who had IVF/intracytoplasmic sperm injection (ICSI) were retrospectively reviewed. Patients were categorized into four groups: previously infected by COVID-19, vaccinated by COVID vaccine, previously infected and vaccinated, or neither infected nor vaccinated. Total number of participants 151 (vaccinated only 66, infected only 18, vaccinated and previously infected 34, and control 33. Outcomes (ET on day of trigger, number of oocytes retrieved, quality of oocytes, number of fertilized oocytes, number and quality of embryos, number of embryos transferred, number of embryos frozen, implantation rate and clinical pregnancy rate) were compared between these four groups. Moreover, we compared the outcome before and post infection, as well as before and post vaccine in a group of patients. No evidence was found to suggest that COVID-19 disease or SARS-CoV-2 Vaccine adversely affects Clinical pregnancy rates (positive fetal heartbeat) (OR 0.9, CI 0.5–1.9, OR 1.8, CI 0.9–3.6, respectively) and the following parameters: fertilization rate, implantation rate, positive bHcg) (OR 0.9, CI 0.5–1.8, OR 1.5, CI 0.7–2.9, respectively). Although a limitation of our study is the small comparison groups, and the wide confidence intervals in the Odds Ratio estimates.

Analysis of factors related to early miscarriage after in vitro fertilization embryo transfer

AimsThis research aims to explore the factors related to early spontaneous miscarriage after in vitro fertilization and embryo transfer (IVF-ET) pregnancy, and to provide guidance for improving pregnancy outcomes. MethodsWe retrospectively analyzed the data for clinical pregnant women (2591 cycles) undergoing IVF-ET at the reproductive center of Peking University People’s Hospital from January 2017 to December 2018; This included 544 ​ET cycles and 2047 frozen embryo transfer cycles. The analysis of factors associated with early miscarriage in the overall population of IVF/intracytoplasmic sperm injection (ICSI) pregnancies (including fresh and thawing cycles) was performed. ResultsThe risk of early miscarriage in the 35–39 age group was 1.35 times higher than that in the <35 age group (OR ​= ​1.35 [1.05,1.73], p ​= ​0.02). In addition, the risk of early miscarriage was 3.88 times higher in the group ≥40 years old than in the group <35 years old (OR ​= ​3.88 [2.68,5.62], p ​< ​0.001). Endometrial thickness also affected the miscarriage rate; the early miscarriage risk with endometrial thickness ≥8.5 ​mm was 0.78 times than that of the <8.5 ​mm group (OR ​= ​0.78 [0.62,0.98], p ​= ​0.03). The early miscarriage rate during frozen embryo transfer was 1.48 times higher than that during fresh embryo transfer (OR ​= ​1.48 [1.08,2.02], p ​= ​0.01), while in the fresh cycle, the risk of early miscarriage with high-quality embryos was 0.5 times lower than that with non-high quality embryos (OR ​= ​0.5 [0.27,0.9], p ​= ​0.02). In the frozen cycle, the risk of early miscarriage in natural cycle transplantation was 0.73 times that in hormone replacement treatment (HRT) cycle transplantation (OR ​= ​0.73 [0.54,0.97], p ​= ​0.03) . ConclusionsAdvanced age is an independent risk factor for early miscarriage, while endometrial thickness at the date of transplantation is an independent protective factor. The risk of early miscarriage in fresh-cycle transplanted embryos is significantly lower than that in frozen embryos, and the number of high-quality embryos in the fresh cycle lowers the miscarriage rate significantly. Natural cycle transplantation has a lower rate of early miscarriage than hormone replacement therapy.

Predicting IVF outcome in poor ovarian responders

BackgroundPoor responders to ovarian stimulation are one of the most challenging populations to treat. As a failed cycle can cause a considerable emotional and economical loss, adequate fertility counseling addressing patients’ expectations are highly important when facing patients with poor ovarian response. The study aimed to evaluate reproductive outcomes and to identify factors associated with live birth (LB) after fresh autologous IVF/intracytoplasmic sperm injection (ICSI) cycles of patients fulfilling the Bologna criteria for poor ovarian response (POR).MethodsA retrospective study included 751 IVF/ICSI treatment cycles which yielded up to three retrieved oocytes, at a tertiary referral hospital between January 2016 and February 2020. A logistic regression analysis was used to adjust for confounders.ResultsClinical pregnancy and LB rate per cycle were significantly higher among women younger versus older than 40 years (9.8% and 6.8% vs 4.5% and 2.1%, p < 0.01, respectively). Patients who achieved LB were significantly younger, had higher number of oocytes retrieved, fertilization rate and top-quality embryos (p < 0.05). Multivariable regression analysis identified patient’s age (OR 0.90; 95% CI 0.845–0.97; p = 0.005) and mean number retrieved oocytes (OR 1.95; 95% CI 1.20–3.16; p = 0.007) as factors significantly associated with the probability of a LB.ConclusionsThe woman’s age and the number of retrieved oocytes are both independent predicting factors of live birth in poor ovarian responders. Considering the risks, the high financial investment and poor reproductive outcomes involved in IVF treatments, raises questions regarding the adequacy of providing treatments in these patients' population. POR younger than 40 years may represent a possible exception due to acceptable probability for a LB.