Differences In Birth Rates Research Articles

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.

Sperm cryopreservation does not affect live birth rate in normozoospermic men: analysis of 7969 oocyte donation cycles.

Does sperm cryopreservation influence the reproductive outcomes of normozoospermic patients in oocyte donation cycles? After controlling for confounders, the use of cryopreserved semen from normozoospermic patients does not affect pregnancy and live birth rates after elective ICSI. Sperm cryopreservation by slow freezing is a common practice in ART. While frozen-thawed semen typically presents reduced motility and vitality, its use for ICSI is generally considered adequate in terms of reproductive outcomes. Nevertheless, most studies comparing reproductive outcomes between fresh and cryopreserved sperm include patients with severe male factor (testicular sperm, oligo-, and/or asthenozoospermia) or women of advanced maternal age, where the altered quality of the gametes can partially mask the full effect of freezing/thawing. The study included a retrospective cohort of 7969 couples undergoing their first oocyte donation cycle between January 2013 and December 2019 in one large clinic, using normozoospermic semen from the male partner. All cycles involved elective ICSI, fresh oocytes, and a fresh embryo transfer, either at cleavage or blastocyst stage. Two study groups were established based on the sperm status: fresh (n = 2865) and cryopreserved (n = 5104). A slow freezing protocol was used for all sperm cryopreservation. Sperm washing, capacitation, and selection prior to ICSI were performed identically for fresh and frozen-thawed samples, using pellet swim-up. Fertilization rate (FR), pregnancy (biochemical and ongoing), and live birth rates were compared between study groups using univariate and multivariate regression analyses. Male and female age, sperm concentration and motility after ejaculation, and number of oocytes inseminated were similar between cycles using fresh or cryopreserved sperm. Analysis by Student's t-test did not indicate a significant difference in FR between fresh and cryopreserved sperm (P = 0.0591); however, after adjusting for confounders, this difference reached statistical significance: 74.65% FR for fresh (CI 95%: 73.92-75.38) versus 73.66% for cryopreserved sperm (CI 95%: 73.11-74.20), P = 0.0334. The adjusted regression analysis revealed higher odds of biochemical pregnancy when using fresh sperm (odds ratio (OR): 1.143, P = 0.0175), but no significant effects of sperm cryopreservation were observed for ongoing pregnancy (OR: 1.101, P = 0.0983) and live birth (OR: 1.082, P = 0.1805). Caution should be exerted when extrapolating these results to different protocols for sperm cryopreservation and selection, or to IVM, advanced maternal age and classical IVF cycles, which were excluded from analysis. Owing to the retrospective nature of the study, some uncontrolled for variables may affect the results. Sperm cryopreservation does not affect pregnancy and live birth rates in normozoospermic patients, and although it may lower FR s slightly, this would not be clinically relevant. In line with previous studies that included patients with an apparent male or female factor, sperm cryopreservation is a safe and convenient technique. The study received no external funding and all authors have no conflicts of interest to declare. N/A.

Predictors and differences in fertility level among Nigerian women of reproductive age: a function of subgroup social norms fertility behaviour

Fertility rates in Nigeria are declining at such a modest rate, that if more proactive measures are not employed to reduce fertility, the nation may double its population before long. We empirically examined fertility behaviour as derivatives of specific subgroup social norms, and the variations in the factors responsible for different fertility behaviours, using the 2018 Nigeria Demographic and Health Survey. Descriptive bivariate, and multinomial logistic regression analyses were used to predict the contribution of demographic and sociocultural factors contributing to the fertility level, and findings were reported as odds ratios. Results revealed that age, religion and level of education are the most significant predictors of fertility level, with remarkable differences in birth rate across subgroups, whereas North-West Nigeria had the highest fertility level. Furthermore, marriage had a significantly negative effect on high fertility among North-Western women, whereas higher education significantly increased high fertility among North-Eastern women. In conclusion, subgroup social norms fertility behaviour is responsible for the persistent fertility differential outcome in Nigeria. Thus, the paper strongly advocates the need to intensify community-led, norm-based solution and not a universal approach in addressing fertility control in Nigeria.

Knockout of HMGA1 Promotes ATRA-Induced Differentiation in MLL-Rearranged Leukemia

Introduction: HMGA1 is a small non-histone chromatin protein characterized by 3 AT-hooks, which modulates transcription by altering the chromatin architecture. It tends to be highly expressed in poorly differentiated cells including hematopoietic stem cells. In various kinds of solid tumors, HMGA1 has been reported to play as an oncogene, and its upregulation was reported to be associated with poorer clinical outcomes. However, although recent study demonstrated that HMGA1 was associated with progression of JAK2V617F positive myeloproliferative neoplasms to myelofibrosis or leukemia, the roles of HMGA1 in myeloid malignancies were still unclear. Therefore, we analyzed its function in myeloid malignancies using HMGA1 knockout (KO) mice. We could not detect clear differences in peripheral blood counts or bone marrow cells, and generated various kinds of models of acute myeloid leukemia (AML). Knockout of HMGA1 could not delay the onset of these leukemia, but we could demonstrate that leukemic cells with MLL-ENL fusion gene which lacked in HMGA1 gene were more susceptible to all-trans retinoic acid (ATRA)-induced expression of CD11b, which suggested that HMGA1 could be associated with the differentiation process induced by ATRA. Method: We generated Vav-iCre HMGA1flox/flox mice, and we first analyzed the fraction of peripheral blood cells and bone marrow cells of these mice using flow cytometry. Next, to evaluate roles of HMGA1 in AML, we made various murine models of AML. We collected c-kit positive fractions of bone marrow cells from the KO mice or Vav-iCre(-) HMGA1flox/flox mice and retrovirally introduced MLL-ENL, MOZ-TIF2, BCL2-MYC fusions. Primary transplantation was performed to sublethally irradiated (5Gy) mice with 4.0×105 infected cells for each fusion gene. Secondary transplantation was also performed for MLL-ENL and BCL2-MYC with 1.0×104 cells for each. Blood samples were collected weekly, and disease-free survivals were compared by Kaplan-Meier method with Vav-iCre(-) HMGA1flox/flox mice. Also, leukemic cells infected with MLL-ENL were collected, and these cells were cultured for four days with different concentrations (1μM, 5μM or 10μM) of ATRA. Flow cytometry analysis was performed to evaluate the differentiation induced by ATRA with antibodies to murine CD11b, c-kit and Gr-1. Result: There was no significant difference in birth rate between Vav-iCre(+) and Vav-iCre(-) mice, which suggested that HMGA1 was not essential for fetal hematopoiesis. Peripheral blood cell counts were measured at week 8 and week 20, and fractions of peripheral blood and bone marrow cells were assessed at week 8 using flow cytometry, but no significant differences were observed. As for AML models, there were no significant differences in survival periods after primary or secondary transplantation. Leukemic cells retrovirally induced with MLL-ENL were collected from primary recipients, and these cells were treated with ATRA. Although growth rates were not show significantly different, expression levels of CD11b after exposure to ATRA were significantly higher in Vav-Cre (+) mice (5μM: 70% vs 44%, respectively; p=0.035. 10μM: 80% vs 46%, respectively; p=0.0006) as shown in the following figure. Discussion: We established HMGA1 KO mice and assessed the function of HMGA1 both in normal and leukemic hemopoiesis. Although HMGA1 might have little effect on normal hematogenesis, it seemed that HMGA1 had inhibitory effect on ATRA-induced differentiation process of MLL-ENL leukemic cells. Though more conditions including AML types and differentiation methods should be tested and the molecular mechanisms should be scrutinized, there is a possibility that inhibition of HMGA1 is effective in combination with differentiation treatments. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Analysis of spatial and temporal impact differences of birth rate in mainland China

The continuing decline in the birth rate has led to a series of problems, such as the disproportion of population structure and severe aging population, which have restricted the country’s economic development. To have a deeper understanding of the geographical differences and influencing factors of the birth rate, this paper collects and organizes the birth population data of 31 provinces in mainland China from 2011 to 2019. The national region is divided into seven natural geographical regions to obtain the spatial hierarchy, and a hierarchical Bayesian Spatio-temporal model is established. The INLA algorithm estimates the model parameters. The results show significant spatial and temporal differences in birth rates in mainland China, which are reflected mainly in the combination of spatial, temporal, and Spatio-temporal interaction effects. In the spatial dimension, the northeast is low, the northwest and southwest are high, and the birth rate has an upward trend from east to west. These trends are caused by unbalanced economic development, different fertility attitudes and differences in fertility security, reflecting regional differences in spatial effects. From 2011 to 2019, China’s birth rate showed an overall downward trend in the time dimension. However, all regions except the northeast saw a significant but temporary increase in birth rates in 2016 and 2017, reflecting the temporal effect difference in birth rates.

Comparison of oocyte count, fertilization, and pregnancy rates in adenomyosis patients undergoing In Vitro Fertilization with short and long protocol controlled ovarian stimulation - Restospective study.

IntroductionAdenomyosis (benign gynecological disease) is an endometrial stromal tissue condition that invades the myometrium of the uterus. The administration of a gonadotropin-releasing hormone (GnRH) analog before the IVF (In Vitro Fertilization) cycle significantly increases the chances of getting pregnant in adenomyosis patient with infertile condition. There is no best protocol consensus for adenomyosis for now. This study plans to compare the outcomes of long-protocol and short-protocol of IVF in adenomyosis patients who have undergone surgery and treatment with GnRH analogs.MethodThis study is a retrospective study with a comparative method. The study was conducted at the IVF Aster Clinic and the IVF Bandung Fertility Center by reviewing retrospective data from 2015 to 2021. Patients who have been diagnosed with adenomyosis will undergo IVF procedure with a long-protocol and short-protocol pretreatment. Parameters observed were oocyte count, fertilization, and pregnancy rate.ResultsFifty-eight patients were included. There was a significant difference in the oocytes count and the pregnancy rate in short and long groups with p value of less than 0.05, while there was no significant difference in fertilization rate with p value of greater than 0.05.ConclusionThere were differences in the oocytes count and pregnancy rates in the short and long protocol groups in adenomyosis patients. There was no difference in fertilization rate in the short and long protocol groups in adenomyosis patients.

Effect of pre-IVF incubation in maturation medium on oocyte maturity, fertilization, embryonic development, and clinical outcomes following embryo transfer

Objective: Collected human cumulus-oocyte complexes (COCs) are usually inseminated after 4 to 6 hours in in vitro fertilization (IVF) laboratories. The purpose of this study was to determine the effect of short-term pre-IVF incubation in culture medium on subsequent oocyte maturation, fertilization, and embryonic development, as well as clinical outcomes. Methods: Sixty patients were divided randomly into 2 groups, pre-IVF incubation for 5 hours: 1) with (+) the designed oocyte maturation medium; 2) without (−) the designed oocyte maturation medium (transferred directly to fertilization medium for 5 hours before insemination). Oocyte maturation and fertilization were assessed, and the rate of cleavage and good quality embryos were evaluated between the 2 groups on days 2 and 3, respectively. Blastocyst development was based on the remaining number of embryos on day 3, continuously cultured to day 5 after embryo transfer or frozen on day 3, and was compared between the 2 groups. Clinical pregnancy, implantation, and miscarriage rates were also compared. Results: Oocyte maturation rates did not differ between groups (85.8 ± 14.1% vs. 90.7 ± 9.1%). However, the range of oocyte maturation rates (58.3%–100.0%) for each patient was significantly higher in the (−) group than in the (+) pre-incubation group (71.4%–100.0%). There were no differences in fertilization rates (89.9 ± 10.0% vs. 86.5 ± 12.2%) and good quality embryos (70.8 ± 19.1% vs. 62.1 ± 23.7%) between groups; however, the blastocyst development rates were significantly different between groups (73.1 ± 20.1% vs. 58.8 ± 18.2%, P &lt;0.05). Nevertheless, clinical pregnancy (62.5% vs. 61.1%) and implantation (46.9% vs. 47.2%) rates did not differ between groups. Conclusions: These results indicate that a short pre-IVF incubation time in the designed culture medium promotes oocyte maturation and embryonic development, suggesting that short pre-IVF incubation of COCs in the designed culture medium may be important for subsequent final oocyte maturation and early embryonic development.

Comparison of Triggering Final Oocyte Maturation with Follicle Stimulating Hormone Plus Human Chorionic Gonadotropin, versus Human Chorionic Gonadotropin Alonein Normoresponder Women Undergoing Intracytoplasmic Sperm Injection: A Randomized Clinical Trial.

Few studies have so far been done about the role of follicle stimulating hormone (FSH) in final oocyte<br />maturation. However, none of these studies have been performed solely on normoresponder patients. This study aimed<br />to determine whether oocyte maturation, as well as fertilization and pregnancy rates, could be improved in normoresponder women with concomitant FSH and human chorionic gonadotropin (hCG) trigger compared to those with the hCG trigger alone.<br />Materials and Methods: In this prospective randomized clinical trial, 117 normoresponder women, aged 19-40 years<br />who were candidates for the gonadotropin-releasing hormone (GnRH) antagonist protocol at Avicenna Infertility<br />treatment Center, were enrolled and claasified in two groups. Final oocyte maturation was triggered using 10000 IU of<br />hCG plus 450 IU of FSH in the first group (59 subjects) and 10000 IU of hCG alone in the second group (58 subjects).<br />The primary outcome was clinical pregnancy rate.<br />Results: Mean age of the patients was 33.21 ± 4.41 years. There was no difference in clinical pregnancy among the<br />two groups (30.9% vs. 25.5%, P=0.525). There was no statistically significant difference in fertilization rate (80.0%<br />vs. 74.1%, P=0.106), implantation rates (18.9% vs. 16.7%, P=0.352), and chemical pregnancy rates (38.2% vs. 32.7%,<br />P=0.550). Oocyte maturation rate (84.2% vs. 73.6%, P<0.001), 2 pronuclei (2PNs) (6.53 ± 2.54 vs. 5.36 ± 2.85,<br />P=0.021) and total embryos (5.85 ± 2.43 vs. 4.91 ± 2.58, P=0.046) were significantly higher in the first group.<br />Conclusion: Adding FSH to hCG for oocyte triggering, significantly improved oocyte maturation rates and total embryos.<br />While there was no significant difference in the clinical and chemical pregnancy rates, between these two groups<br />(registration number: IRCT20190108042285N1).

P-457 Spindle transfer rescues poor embryo development of in vitro matured ovarian tissue oocytes from transgender men

Abstract Study question Could collection temperature and spindle transfer (ST) potentially improve development of embryos derived from in vitro matured (IVM) ovarian tissue oocytes (OTO) of transgender men? Summary answer Spindle transfer, but not collection temperature, significantly improved embryo development of OTO-IVM oocytes from transgender men. What is known already For transgender men, the fertility preservation strategy of ovarian stimulation may interfere with the desired masculine characteristics and enhance gender dysphoria. Alternatively, ovarian tissue oocytes collected ex vivo could serve as potential gametes, not requiring ovarian stimulation. Oocytes can be collected during gender affirming surgery, matured, and vitrified. Ovarian tissue oocyte in vitro maturation (OTO-IVM) has successfully been used for cancer patients, as live births have been reported. OTO-IVM in transgender men demonstrated sufficient maturation rates and survival following vitrification. Nevertheless, a decreased fertilization potential of these oocytes and severely compromised embryonic development have been observed. Study design, size, duration Patients between 18-24 years were recruited for this study from November 2020 to September 2021. Ovaries from 14 transgender men were collected in either cold (4oC, OTO-Cold) or warm (37oC, OTO-Warm) collection medium, to verify the best collection method. Following ovarian manipulation, cumulus oocyte complexes (COCs) were harvested from spent medium and underwent maturation for 48hrs. ST was performed to overcome inferior fertilization and embryonic development. Participants/materials, setting, methods Injected IVM oocytes underwent calcium imaging or were monitored for embryonic developmental potential. In vitro matured GV (germinal vesicle), MI (metaphase I) and in vivo matured oocytes with clusters of smooth endoplasmic reticulum (SERa) served as controls and cytoplasmic recipients for ST. OTO-IVM or control oocytes were used as spindle donors (ST-OTO or Control-ST respectively). Genetic analysis was performed to detect chromosomal abnormalities in embryos from all groups. Main results and the role of chance In total, we collected 252 OTO-Cold and 230 OTO-Warm oocytes, showing similar maturation rates (53%). For calcium imaging, 39 control, 33 OTO-cold and 31 OTO-warm oocytes were analysed, determining the product of amplitude per frequency, in arbitrary units (AU). The average value for control oocytes was 2.30AU, significantly higher than OTO-Cold (1.47AU, p=0.046) and OTO-Warm oocytes (1.03AU, p=0.036). Calcium release was similar between OTO-Cold and OTO-Warm oocytes. Following ICSI, 19/47 OTO-Cold and 24/48 OTO-Warm oocytes normally fertilized, significantly lower than the control group (42/52) (p &amp;lt; 0.001 and p = 0.001 respectively). Blastocyst formation was significantly higher in control oocytes (13/42,31%) when compared to OTO-Cold (1/19, p=0.027) and OTO-Warm (2/24, p=0.035). No statistically significant difference in fertilization rate and embryo development was detected between OTO-Cold and OTO-Warm oocytes. ST was performed to overcome poor embryo development in the OTO-Cold group. Following ST, 12/19 ST-OTO-Cold and 24/38 Control-ST oocytes were normally fertilized. Blastocyst development was similar between the two groups (4/12 and 7/24 respectively), but significantly higher than blastocyst development in OTO-Cold ICSI oocytes (p = 0.038 and p = 0.045). Genetic analysis revealed that 4/10 OTO-Cold, 4/11 OTO-Warm, 4/11 ICSI control, and 4/7 Control-ST embryos were chromosomally abnormal while 6/8 OTO-ST were abnormal, and 2/8 showed a suggestive low-grade mosaicism. Limitations, reasons for caution A major limitation of our study is the lack of ovaries from cis women. Control oocytes used in this study originate from infertility patients that underwent ovarian stimulation. High abnormality rate in ST-OTO embryos might be concerning for the safety of ST, but the number of embryos analysed is limited. Wider implications of the findings Our data indicate that OTO-IVM oocytes from transgender men display poor cytoplasmic quality, demonstrated by embryonic arrest and calcium imaging. ST was able to overcome poor embryo development, and it could be of interest to use freshly donated oocytes as cytoplasmic recipients for this. Trial registration number Not applicable

P-027 which is the best method of testicular sperm retrieval for NOA? an answer from 1071 TESE cases in my clinics over 25 years

Abstract Study question Which improves sperm recovery rate (SRR) for men with non-obstructive azoospermia (NOA), microdissection TESE (m-TESE) or conventional TESE (c-TESE)? Summary answer SRR of c-TESE vs. m-TESE for NOA was not significant. We need to develop a safer, less-invasive technique with fewer complications and higher SRR. What is known already m-TESE has been performed for men with NOA since Schlegel P’s report (Hum Reprod, 1999). Seminiferous tubules containing many developing germ cells were likely to be larger and more opaque and the ability to find spermatozoa increased from 45% (10/22) to 63% (17/27) after introduction of the microdissection technique. However, Jarvis S et al. (Turek PG group, 2019) reported that at least one site revealed mature sperm in 24 (29.3%) of 82 men with prior failed micro TESE procedures, and sperm were more likely to be found in the testis periphery rather than centrally with FNA mapping. Study design, size, duration TESE was performed in 1071 azoospermic patients in my clinics; c-TESE was performed for all azoospermic patients between 1996 and 2005 in Sendai; c-TESE for OA and m-TESE for NOA was performed from 2006 in Sendai, and from 2012 in Takanawa. The patients were divided into four groups; 1) FSH≦9.2mIU/ml, Testicular volume(TV)≧15/ml (OA), 2) FSH≦9.2mIU/ml, TV &amp;lt; 15ml, 3) FSH&amp;gt;9.2mIU/ml, TV≧15ml, 4) FSH&amp;gt;9.2mIU/ml, TV &amp;lt; 15ml (NOA). Participants/materials, setting, methods c-TESE was performed in 178 azoospermic men (50, 12, 7, 109, respectively) in 1996-2005. c-TESE was performed in 181 patients (131, 26, 15, 9, respectively) and m-TESE was performed in 541 patients (56, 33, 35, 416, respectively) in 2006 -2020. SRR, pregnancy rate (PR), and birth rate (BR) in 1996-2005 were compared with those in 2006-2020. Main results and the role of chance Statistical analysis was performed by chi-square analysis. SRR in c-TESE was 96.0% (48/50) in group 1 (OA) vs. 36.7% (40/109) in group 4 (NOA) in Sendai between 1996 and 2005 (P &amp;lt; 0.001). SRR of c-TESE was 36.7% (40/109) in group 4 (NOA, in Sendai, 1996-2006), whereas SRR of m-TESE was 31.3% (130/416) in group 4 (NOA, in Sendai and Takanawa, 2006-2020). There was no significant difference (np). Total SRR of conventional TESE for all azoospermic patients between 1996 and 2005 was 54.9% (96/175), whereas total SRR of c-TESE for OA and m-TESE for NOA between 2006 and 2020 was 51.7% (373/721). NOA rate 4) of azoospermic patients of 1996-2005 and that of 2006-2020 was 61.2% (109/178) and 58.9% (425/721), respectively. There was no significant difference (np). PR was 37.4% (61/163) and BR was 31.9% (52/263) in c-TESE (1996-2005), PR was 39.6% (388/980), and BR was 27.6% (270//980) in both c-TESE and m-TESE (2006–2020). There was a significant difference in birth rate (P &amp;lt; 0.05). In conclusion, SRR, PR, and BR were not improved even after m-TESE was performed. Considering the fact that m-TESE cannot find sperm thoroughly, adopting other techniques such as sperm fine-needle aspiration may be required. Limitations, reasons for caution Not applicable. Wider implications of the findings We could not show the effectiveness of m-TESE compared with c-TESE. However, the total volume of seminiferous tubules collected by c-TESE was the higher. The new one-step fine-needle aspiration has the potential to achieve higher sperm yield with fewer complications. Further advanced technology will hopefully improve the SRR in NOA. Trial registration number none

P-096 Clinical outcome of ICSI, PICSI and testicular spermatozoa-ICSI procedures in overcoming in patients with high level of sperm DNA fragmentation

Abstract Study question To compare the clinical effectiveness of ICSI, PICSI and testicular spermatozoa-ICSI (T-ICSI) in patients with abnormal level of sperm DNA fragmentation (SDF). Summary answer Clinical effect of T-ICSI procedure exceeds the effect of PICSI and ICSI in male infertility with high level of SDF. What is known already The effectiveness of ART in male infertility depends on sperm chromatin structure integrity. High level of SDF may be reason of IVF/ICSI procedure failures. Several studies have demonstrated impaired clinical outcomes of ICSI in patients with abnormal level of SDF. SDF has a positive correlation with pregnancy loss. It has been shown the benefit of using of testicular spermatozoa in ICSI in high level of SDF. PICSI is a method of the selection of sperm that may reduce the risk of reproductive losses. The data on the comparison of the effectiveness of these methods in high SDF are limited. Study design, size, duration Data was collected from 2019 to 2021 years. The couples with male factor of infertility were enrolled in the study. All the patients had abnormal level of SDF (30-45%). The age of women was less than 35 year. The couples were randomly selected and divided in 3 groups according the ART method: I (n = 25) ICSI; II (n = 22) PICSI; III (n = 20) T-ICSI procedure. Participants/materials, setting, methods The trial involved 67 couples. The mean patients age was 33,3±6,2 y (24-46), the women age - 29,1±2,3 (25-33). All of the men were non-smokers, had idiopathic pathospermia, high level of SDF and underwent unsuccessful courses of empirical therapy in anamnesis. SDF level was measured by TUNEL method. 52 (77,6%) couples had unsuccessful attempts of ICSI including pregnancy loss. The fertilization, blastocyst formation (Gr A/B), clinical pregnancy and live birth rates were measured. Main results and the role of chance It was not significant difference in SDF level in the groups: I group - 37,3±3,1%; II group - 37,2±3,5%; III group - 37,8±3,2% (III). The fertilization rate was comparable in the groups I, II and III - 65,4%; 66,6%; 63,3% respectively. Blastocyst formation (good quality embryos) rate was 41,2%; 46,1%; 56,1%(p &amp;lt; 0001) in I, II and III groups respectively. Clinical pregnancy and life birth rates were 36,0% [9/25]; 40,9%[9/22] (p &amp;lt; 0,05); 45,0%[9/20] (p &amp;lt; 0001) and 20,0% [5/25]; 27,2%[6/22]; 35%[7/20] in ICSI, PICSI, T-ICSI groups respectively. It was significant difference in miscarriage rate 16%, 13,7% (p &amp;lt; 005), 10% (p &amp;lt; 0001) in I, II и III groups respectively. Limitations, reasons for caution T-ICSI might compensate for ART failure in high level of SDF cases. Testicular sperm retrival is an invasive intervention, and its benefit must be carefully justified in each cases. Further studies are needed to determine whether infertility with sperm DNA damage can be overcomed by less invasive methods than T-ICSI. Wider implications of the findings There was no significant difference in fertilization rate in ICSI, PICSI and T-ICSI. T-ICSI demonstrated the best blastocyst formation rate and clinical outcome in trial. According results of our investigation PICSI might increase pregnancy rates and reduce pregnancy losses when compared with ICSI in infertility in high SDF. Trial registration number not applicable

P-082 Microfluidic-based device selects sperm with less DNA damage and higher motility, what else?

Abstract Study question Does the microfluidic-based sperm selection device ZyMōt improve sperm parameters and other laboratory key performance indicator (KPI) values compared to the conventional swim-up method? Summary answer The microfluidic-based sperm selection device ZyMōt selects sperm with lower DNA fragmentation and higher motility than conventional swim-up method in intracytoplasmic sperm injection (ICSI) cycles. What is known already Elevated levels of sperm DNA fragmentation (SDF) in semen samples have been associated with poor embryo development and low pregnancy rates. SDF refers to breaks in the sperm's genetic material, mainly due to defects during spermatogenesis and other factors such as reactive oxygen species that are favored by centrifugation. Conventional sperm selection methods, by integrating centrifugation into their protocols, have become ineffective in selecting sperm with low SDF. In order to solve this problem and improve reproductive outcomes, microfluidic-based devices such as ZyMōt have been designed to avoid centrifugation and select spermatozoa with low SDF. Study design, size, duration Prospective, experimental, single-center study conducted from June to December 2021. A total of 14 couples with ≥ 10 retrieved oocytes were recruited for an intra-patient comparison. Semen sample was split and processed for ICSI by the conventional swim-up method or by the microfluidic-based device ZyMōt. Each fraction was used to fertilize half of the total number of oocytes retrieved. SDF index, semen parameters, useful blastocyst rate, fertilization rate and morphokinetic variables were observed. Participants/materials, setting, methods Oocytes retrieved were from own (n = 96) and donation cycles (n = 93). From each patient, the cohort of oocytes was divided into two groups: 1) inseminated with spermatozoa selected by swim-up and 2) inseminated with spermatozoa selected by ZyMōt 850 µL device. Embryo evaluation and development were then followed by time-lapse monitoring using EmbryoScope. Sperm chromatin dispersion (SCD) assay was used to measure SDF, analyzed by ImageJ. Each treatment followed routine protocol established in the clinical practice. Main results and the role of chance SDF index was significantly lower in ZyMōt group in comparison with swim-up group (10% vs 20%), indicating a better selection by the ZyMōt of sperm with less DNA breaks. Additionally, ZyMōt group also presented a significantly greater number of spermatozoa with progressive motility (96.9% vs 95.4%). In contrast, useful blastocyst rate showed a slightly, but not significantly, increment in ZyMōt group compared to swim-up group (53.2% vs 46.6%). No significant differences in fertilization rate or sperm recovery rate were observed between groups. Regarding morphokinetic parameters, timing variables from first cell division to blastocyst stage (t2-tB) showed no significant correlation with ZyMōt group contrasted with swim-up. Blastocysts were evaluated and a value was assigned with respect to their quality (A to D). There was a higher number of embryos with A grade in ZyMōt group and a higher number of embryos with D grade in swim-up group. The annotated variables were assessed using paired t-test and P value &amp;lt;0.05 was considered statistically significant. Limitations, reasons for caution The impact on reproductive outcomes may vary depending on whether the breakage is single- or double-stranded, however, SCD is not able to distinguish between them. These, together with the oocyte's ability to repair sperm damage, lead us to the explanation for the non-significance on embryo quality. Wider implications of the findings This study provides further insights into the use of ZyMōt for the selection of low SDF spermatozoa in a simple manner. Its use could be indicated in patients with a high SDF value in their semen samples. Benefits on reproductive outcome will be confirmed with larger sample size. Trial registration number 2102-VLC-007-MD

Socioeconomic Disparity in Birth Rates During the COVID-19 Pandemic in New York City.

Background: The differential impact of the coronavirus disease 2019 (COVID-19) pandemic across race, ethnicity, and socioeconomic status remains poorly understood. While recent explorations into birthrates during the pandemic have revealed significant declines, how birthrates may have differed between racial and socioeconomic subgroups during the pandemic remains to be detailed. Methods: Using electronic health records from a large hospital network in New York serving a racially and socioeconomically diverse population, we explored birthrates associated with conceptions that occurred during the COVID-19 pandemic lockdown for demographic and obstetric differences. Results: Two thousand five hundred twenty-three unique patient deliveries corresponded with conceptions that occurred during the COVID-19 pandemic lockdown in New York. Compared to the same period the previous year, there was a 22.85% decrease in births. Explorations into differences in birthrates by socioeconomic status revealed that much of the decline could be explained by fewer births among individuals living in higher socioeconomic status as opposed to individuals living in urban economic poverty [χ2(n = 5588) = 18.35, p < 0.01]. Conclusion: On March 22, 2020, New York instituted a prohibition of all nonessential social gatherings and the closure of all nonessential businesses. Although the full impact of the COVID-19 pandemic on reproductive health and outcomes remains largely unknown, the decreased birthrate associated with the initial COVID-19 wave in New York was not entirely unexpected. While the mechanisms that drive health disparities are complex and multifactorial, most of the decrease occurred among those living in higher socioeconomic status. This finding has important implications for understanding health behaviors and disparities among minorities living in low socioeconomic status.

Effect of A23187 ionophore treatment on human blastocyst development-a sibling oocyte study.

To investigate whether treatment with commercially available ready-to-use A23187 ionophore (GM508-CultActive) improves embryo development outcome in patients with a history of embryo developmental problems. This is a uni-center prospective study in which sibling oocytes of patients with embryos of poor quality on day 5 in the previous cycle were treated or not with CultActive. Two hundred forty-seven metaphase II (MII) oocytes from 19 cycles performed between 2016 and 2019 were included in the study. After ICSI, the sibling oocytes were assigned to the treatment group or to the control group, following an electronically generated randomization list. A number of 122 MII were treated with CultActive and 125 MII had no treatment and were assigned to the control group. No difference in fertilization rate (p = 0.255) or in the capacity of embryos to reach good quality on day 5 (p = 0.197) was observed between the two groups. The utilization rates defined as the number of embryos transferred or cryopreserved per mature oocyte (p = 0.438) or per fertilized oocytes (p = 0.299) were not significantly different between the treated group and the control group. The results of the current study do not support the use of CultActive in cases with embryo developmental problems.

Epilepsy and Pregnancy.

Seizure disorders are the most frequent major neurologic complication in pregnancy, affecting 0.3% to 0.8% of all gestations. Women of childbearing age with epilepsy require special care related to pregnancy. This article provides up-to-date information to guide practitioners in the management of epilepsy in pregnancy. Ongoing multicenter pregnancy registries and studies continue to provide important information on issues related to pregnancy in women with epilepsy. Valproate poses a special risk for malformations and cognitive/behavioral impairments. A few antiseizure medications pose low risks (eg, lamotrigine, levetiracetam), but the risks for many antiseizure medications remain uncertain. Although pregnancy rates differ, a prospective study found no difference in fertility rates between women with epilepsy who were attempting to get pregnant and healthy controls. During pregnancy, folic acid supplementation is important, and a dose greater than 400 mcg/d during early pregnancy (ie, first 12 weeks) is associated with better neurodevelopmental outcome in children of women with epilepsy. Breastfeeding is not harmful and should be encouraged in women with epilepsy even when they are on antiseizure medication treatment. Women with epilepsy should be counseled early and regularly about reproductive health. Practitioners should discuss the risks of various obstetric complications; potential anatomic teratogenicity and neurodevelopmental dysfunction related to fetal antiseizure medication exposure; and a plan of care during pregnancy, delivery, and postpartum. Women with epilepsy should also be reassured that the majority of pregnancies are uneventful.

Comparison of Triggering Final Oocyte Maturation with Follicle Stimulating Hormone Plus Human Chorionic Gonadotropin, versus Human Chorionic Gonadotropin Alonein Normoresponder Women Undergoing Intracytoplasmic Sperm Injection: A Randomized Clinical Trial

Background:Few studies have so far been done about the role of follicle stimulating hormone (FSH) in final oocyte maturation. However, none of these studies have been performed solely on normoresponder patients. This study aimed to determine whether oocyte maturation, as well as fertilization and pregnancy rates, could be improved in normoresponder women with concomitant FSH and human chorionic gonadotropin (hCG) trigger compared to those with the hCG trigger alone.Materials and Methods:In this prospective randomized clinical trial, 117 normoresponder women, aged 19-40 years who were candidates for the gonadotropin-releasing hormone (GnRH) antagonist protocol at Avicenna Infertility treatment Center, were enrolled and claasified in two groups. Final oocyte maturation was triggered using 10000 IU of hCG plus 450 IU of FSH in the first group (59 subjects) and 10000 IU of hCG alone in the second group (58 subjects). The primary outcome was clinical pregnancy rate.Results:Mean age of the patients was 33.21 ± 4.41 years. There was no difference in clinical pregnancy among the two groups (30.9% vs. 25.5%, P=0.525). There was no statistically significant difference in fertilization rate (80.0% vs. 74.1%, P=0.106), implantation rates (18.9% vs. 16.7%, P=0.352), and chemical pregnancy rates (38.2% vs. 32.7%, P=0.550). Oocyte maturation rate (84.2% vs. 73.6%, P<0.001), 2 pronuclei (2PNs) (6.53 ± 2.54 vs. 5.36 ± 2.85, P=0.021) and total embryos (5.85 ± 2.43 vs. 4.91 ± 2.58, P=0.046) were significantly higher in the first group.Conclusion:Adding FSH to hCG for oocyte triggering, significantly improved oocyte maturation rates and total embryos. While there was no significant difference in the clinical and chemical pregnancy rates, between these two groups (registration number: IRCT20190108042285N1).

Tricostatin A-treated round spermatid enhances preimplantation embryo developmental competency following round spermatid injection in mice.

It has been documented that the inefficacy of round spermatid injection (ROSI) might be caused by abnormal epigenetic modifications. Therefore, this study aimed to evaluate the effect of trichostatin A (TSA) as an epigenetic modifier of preimplantation embryo development in activated ROSI oocytes. Matured oocytes were collected from superovulated female mice. Testes were placed in human tubal fluid medium and masses were then cut into small pieces to disperse spermatogenic cells. Round spermatids were treated with TSA and subsequently injected into oocytes. The expression level of the development-related genes including Oct4, Sox2, Nanog, Dnmt and Hdac transcripts were evaluated using qRT-PCR. Immunohistochemistry was performed to confirm the presence of Oct-4 protein at the blastocyst stage. There was no statistically significant difference in fertilization rate following ROSI/+TSA compared with the non-treated ROSI and intracytoplasmic sperm injection (ICSI) groups. Importantly, TSA treatment increased blastocyst formation from 38% in non-treated ROSI to 68%. The relative expression level of developmentally related genes increased and Dnmt transcripts decreased in ROSI/+TSA-derived embryos, similar to the expression levels observed in the ICSI-derived embryos. In conclusion, our results indicate that spermatid treatment with TSA prior to ROSI would increase the success rate of development to the blastocyst stage and proportion of pluripotent cells.

EFFECT OF MORPHOLOGICAL ABNORMALITIES OF PROTRUDING AND STRATIFIED ZONA PELLUCIDA ON FERTILIZATION RATE

In general, oocyte maturation is judged by the presence or absence of the first polar body. However, there are cases in which it is difficult to determine the released polar body due to morphological abnormalities of the zona pellucida. We have reported cases of pregnancy and delivery from oocytes with abnormal zona pellucida, which are characterized by protruding or stratified zona pellucida and a narrow perivitelline space. However, since the potential effect of zona pellucida abnormalities on fertilization rate has not been clarified, we compared the fertilization rate of oocytes with and without zona pellucida abnormalities. In addition, since there were oocytes with different shapes of the zona pellucida, such as protruding or stratified, we compared the difference in fertilization rates for each morphological group. In this study, we examined 218 MII stage oocytes among 12 patient cases with abnormal zona pellucida retrieved at our clinic from January 2013 to December 2019, and compared the normal fertilization rate of ICSI and IVF with that of 186,534 MII stage oocyte from 10,444 cases without abnormal zona pellucida retrieved during the same period. The oocytes that showed zona pellucida abnormalities were classified into two groups: those with protruding zona pellucida and those with stratified zona pellucida, and the normal fertilization rates were compared. Test for significance differences was performed using the chi-square test. The normal fertilization rates of oocytes with abnormal zona pellucida were 61.4% for ICSI(124/202) and 6.3% for IVF(1/16), which were significantly lower than those of oocytes without abnormal zona pellucida, which were 80% for ICSI(126685/158309) and 65% for IVF(18356/28225). (P<0.05) When comparing oocytes with abnormal zona pellucida, the normal fertilization rates were 60.7% (51/84) for protruding oocytes and 63.6% (70/110) for stratified oocytes, with no significant difference between the two groups. The fertilization rate in cases with abnormal zona pellucida is significantly lower than in cases without abnormal zona pellucida. This may be due to the fact that the polar body is difficult to see due to the narrow perivitelline space, and therefore the oocytes that cannot be accurately judged for maturity may be fertilized. In addition, there was no difference in fertilization rate between the two groups of protruding and stratified oocytes, suggesting that the difference in shapes does not affect the fertilization results.

DOES ZYMŌT SPERM SEPARATION IMPROVE EMBRYO DEVELOPMENT OUTCOMES WHEN APPLIED TO ALL INFERTILITY PATIENTS COMPARED TO DENSITY GRADIENT WASHING OR SURGICALLY ATTAINED SPERM?

The ZyMōt sperm separation device has proven favorable for use in elevated DNA fragmentation index (DFI) male factor patients, as an alternative to density gradient (DG) washing or surgically attained testicular sperm. In 2020, without fully understanding the infectivity and transmission potential of SARS-CoV2 in semen, a more liberal application of a timed ZyMōt microfluidic swim-up was applied to our IVF patients to dilute out and minimize potential pathogens. This study aimed to evaluate whether the use of ZyMōt sperm improved normal embryo development. Retrospective analysis of PGT-A/ICSI cycles (N= 3219) between 2016-2020 was conducted to assessed fertilization rates (FR), blastocyst development/utilization rates (BUR) and genetic outcomes. Sperm preparations were performed per standard operating or manufacturer advised (i.e., ZyMōt) procedures. Cumulus oocyte complexes were harvested 36h post-hCG, stripped and ICSI performed 3-5hr later. Zygotes were assessed at 16-18hr post-ICSI, and embryos cultured under humidified tri-gas incubation for up to 7 days. Blastocyst (BL) development as evaluated, and expanded BL or greater were biopsied on Days 5, 6 or 7. All BL were vitrified and genetics determinations for euploidy, aneuploidy and mosaicism were contrast. Applying Chi-squared analysis, we compared potential differences (p<0.05) between oocytes inseminated by DG wash (n=23,549), ZyMōt wash (n=7,331) or testicular sperm (n=815). No difference in FR (76%), D5 BL formation (52-56%) or BUR (52-53%) was detected between DG and ZyMōt washed sperm, respectively. Meanwhile, testicular sperm had a lower FR (70%; p<0.05), fewer BL forming on D5 (48%; p<0.05) and a lower overall BUR (41%; p<0.05). In addition, fewer testicular-derived BL were euploid (39%; p<0.05) with more aneuploidy (54%; p<0.05) than DG wash (50%, 39%; respectively) or ZyMōt swim-up (45%, 37%; respectively) derived-embryos. No difference in potentially viable BL (Euploidy+Mosiac outcome) was observed between DG or ZyMōt wash groups (63-64%). Application of the ZyMōt device in the general IVF population offered no benefit to embryo development outcomes compared to standard sperm wash procedures. Our data does support that microfluidic separation of sperm using ZyMōt for male factor patients with elevated DFI is a more favorable and cost-effective approach to surgically attaining testicular sperm when ejaculated sperm is possible. However, when insufficient motile and or morphologically normal sperm are available in an ejaculate further analysis is needed to elucidate the benefit of testicular biopsy treatment, as our assessments in this study may be biased by including men with non-obstructive azoospermia.

P–045 A retrospective study on Hyaluronic acid binding sperm selection in ICSI cycles

Abstract Study question Does Hyaluronic acid(HA) binding sperm selection prior ICSI produce better outcome compare to PVP? Summary answer No significant difference in fertilization rate, blastocyst utilization rate, pregnancy rate and miscarriage rate in HA vs PVP group. What is known already HA is natural, non-sulphated glycosaminoglycan secretion that abundantly found in the cervical mucus and the cumulus oophorus complex (COC). In in-vivo, HA binding sites on the sperm plasma membrane indicate sperm maturity, mature sperm reaching HA-coated COC can bind and digest HA and subsequent hyperactivation further facilitate fertilization. In IVF, the use of HA tries to mimic in-vivo to select mature sperm with high DNA integrity prior to ICSI. In HA, movement of mature sperm is ‘slowed’ thus allow the selection of sperm to be used in ICSI. Sperm immaturity is known to associated with aneuploidy incidence in the embryos. Study design, size, duration ICSI cycle using HA (N = 83) was adapted from January to December 2020 while ICSI cycle using PVP (N = 133) was adapted from January 2018 to December 2019. Mean age of patient were 35.64±4.33 vs 34.15±4.75 for HA vs PVP group respectively. Fertilization rate, blastocyst utilization rate, pregnancy rate and miscarriage rate were recorded. This study included all ICSI cycle and both frozen and fresh embryo transfer data. Surgical retrieved sperm was excluded from this study. Participants/materials, setting, methods A 1.5ul of treated spermatozoa suspension was connected with a pipette tip to a 5ul droplet of fresh holding medium (Cook Gamete Buffer). Simultaneously, a 5ul droplet of HA medium (Origio SpermSlow) was connected to the 5ulL droplet of holding medium in a ICSI dish (Sparmed Oosafe) covered with oil (Vitrolife Ovoil). Sperm which were ‘slowed’ in the Sperm slow droplets with normal morphology according to WHO 2010 guideline were selected for ICSI at 400X. Main results and the role of chance The fertilization rate of the HA vs PVP- binding sperm are 68.6% vs 66.2%. As for the blastocyst utilisation rate is 61.6% vs 73.22% for HA vs PVP- binding sperm group. Pregnancy and miscarriage rate for HA vs PVP are 42.3% vs 51.5% and 19.4% vs 26.2% respectively. There was no significant difference in the fertilization rates, blastocysts utilisation rate, pregnancy rate and miscarriage rate between the HA vs PVP- binding sperm groups (P &amp;lt; 0.05). However, a trend of higher pregnancy (51.5% vs 42.3%; P = 0.279) and miscarriage rate were observed in the PVP group (26% vs 19%; P = 0.545) as compared to the HA group, but the difference was not statistically significant. The reason behind this might be the HA assist to select the mature sperm with higher DNA integrity and low frequency of chromosomal aneuploidies which contribute to the lower miscarriage rate in the study. Limitations, reasons for caution This is a retrospective study on HA binding sperm selection vs PVP prior to ICSI. Further research which includes a large number of RCT sample size should be warranted. Wider implications of the findings: The HA- sperm binding selection ICSI might only be beneficial to certain group of patients (high- DNA fragmentation sperm). A larger RCT study may be necessary to establish a relationship between HA-sperm binding selection vs aneuploidy rate via PGT analysis. Trial registration number Not applicable