Intracytoplasmic Sperm Injection Group Research Articles

45 Does ovarian endometriosis increase oocyte sensitivity to icsi-induced mechanical damage?

Introduction and aims of the study: Some studies on sibling oocytes have shown that intracytoplasmic sperm injection (ICSI) obtains poorer results than conventional in vitro fertilization (cIVF) in women with ovarian endometriosis, suggesting that their oocytes could be particularly sensitive to some ICSI-induced mechanical damage. Aims of this study were to clarify (a) whether ovarian endometriosis could induce peculiar fragility in the oocytes of women with endometriosis, so that ICSI would finally result harmful, and (b) whether endometrioma removal before IVF could be advisable in order to avoid any hypothetical detrimental effect on oocytes. Methods: In the present case-control study, data of women who underwent their first IVF cycle between January 2010 and December 2018 at the IVF Unit of S. Anna Hospital, Turin (Italy), were retrospectively reviewed. We included 368 women: 203 with in situ endometrioma at the time of IVF (128 of which underwent ICSI and 75 cIVF), and 165 who received laparoscopic stripping of endometrioma before undergoing ICSI. Results: For women with in situ endometrioma at the time of treatment, ICSI and cIVF outcome was comparable for all studied parameters, including the clinical pregnancy rate per embryo transfer (PR/ET: 31.8% (95% confidence interval (CI), 20.8-44.4%) in cIVF group vs. 39.5% (95%CI, 30.7-48.9%) in ICSI group, p=0.15) and the cumulative live birth rate per ovum pick-up (CLBR/OPU: 24.4% (95%CI, 15.6-35.1%) in cIVF group vs. 27.7% (95%CI,20.7-35.7%) in ICSI group, p=0.29). ICSI outcome was also similar comparing women with in situ endometrioma (CLPR/OPU: 27.7% (95%CI, 20.7-35.7%)) and women previously submitted to laparoscopic stripping of the ovarian cyst (CLPR/OPU: 25.1% (95%CI, 19.1-32.0%)) (p=0.30). Conclusions: Our findings suggest that (a) in women with in situ endometrioma ICSI may be performed, when needed, without harming oocytes and compromising the outcome, and (b) there is no advantage in removing endometrioma before performing ICSI.

Non-Assisted Hatching Trophectoderm Biopsy Does Not Increase The Risks of Most Adverse Maternal and Neonatal Outcome and May Be More Practical for Busy Clinics: Evidence From China

ObjectiveThis study was conducted in order to investigate whether non-assisted hatching trophectoderm (TE) biopsy increases the risks of adverse perinatal outcomes in livebirths following elective single cryopreserved-thawed blastocyst transfer.Patients and MethodsA total of 5,412 cycles from 4,908 women who achieved singleton livebirths between 2013 and 2019 were included in this retrospective cohort study. All embryos in this study were fertilized by intracytoplasmic sperm injection (ICSI) and cryopreserved through vitrification. The main intervention is to open the zona pellucida (ZP) of day 5/6 blastocyst immediately for biopsy without pre-assisted hatching. The main outcome measures are the common maternal and neonatal outcomes, including hypertensive disorders of pregnancy (HDPs), gestational diabetes mellitus (GDM), abnormal placentation, abnormalities in umbilical cord and amniotic fluid, preterm birth, cesarean section, low birth weight, postpartum hemorrhage, and prolonged hospital stay (both mothers and infants). The generalized estimation equation (GEE) was used to control the effects of repeated measurements. The non-conditional logistic regression model was used to examine the associations between embryo biopsy status and each adverse perinatal event. Given that the selection bias and changes in learning curve might affect the results, we selected 1,086 similar (matching tolerance = 0.01) cycles from the ICSI group via propensity score matching (PSM) for second comparisons and adjustment (conditional logistic regression).ResultsAfter adjusting for confounders, we confirmed that the non-assisted hatching protocol did not increase the risks of most adverse maternal and neonatal outcomes. Despite this, there were increased risks of GDM (aOR: 1.522, 95% CI: 1.141–2.031) and umbilical cord abnormalities (aOR: 11.539, 95% CI: 1.199–111.067) in the biopsy group. In the second comparisons after PSM, GDM incidence in the biopsy group was still higher (7.26% vs. 5.16%, P = 0.042), yet all measurement outcomes were equally likely to occur in both groups after the second adjustment.ConclusionsThe non-assisted hatching TE biopsy does not increase the risks of most adverse perinatal outcomes. However, there is a higher GDM incidence in the biopsy group, and this association warrants further study. Considering its safety and simplicity, the non-assisted hatching protocol has the potential to become the preferred option for TE biopsy, especially in busy clinics and IVF laboratories.

Does Testicular Sperm Alter Reproductive and Perinatal Outcomes in Assisted Reproductive Technology Cycles? 10 Years' Experience in an Indian Clinic.

Intra-Cytoplasmic Sperm Injection (ICSI) has revolutionized the reproductive outcomes for couples with male factor infertility. Especially in azoospermic men, use of ICSI with surgically retrieved testicular sperm has helped them have their own biological child. However, considering the immature nature of testicular sperm safety of testicular sperm has been debated. To compare reproductive outcomes, neonatal outcomes and the incidence of congenital malformations in children born after intracytoplasmic sperm injection (ICSI), using different sperm origins. This is a retrospective study in which a total of 989 participants were enrolled. Study group (Testicular Sperm Aspiration (TESA) ICSI group) had 552 couples with female partners aged ≤37 and had self gamete cycles. ICSI cycles with ejaculated sperm (EJS) acted as the control group. All male patients underwent surgical sperm retrieval and all the women underwent controlled ovarian stimulation and transvaginal oocyte retrieval and Ovum Pick Up (OPU) as per the standard operating procedures of the clinic. Frozen embryo transfer with two good-grade blastocysts, which had shown 100% survival, were transferred in subsequent cycles. The Student's t-test was performed for age distribution; odds ratio was performed to find the confounding factors. Embryonic and reproductive outcomes were comparable and not statistically significant in the study and control groups. Incidence of congenital anomalies was observed in singleton live births and twin live births in both the TESA-ICSI group and the EJS-ICSI group, but the difference was not statistically significant. Our study revealed that congenital malformations in children born out of ICSI using testicular sperm and EJS were similar; no difference was observed in miscarriages between the testicular sperm-ICSI and EJS-ICSI group. Our data suggests that surgical sperm retrieval in couples with male factor infertility does not alter their reproductive outcome.

High survival of bovine mature oocytes after nylon mesh vitrification, as assessed by intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is an alternative technique to in vitro fertilization (IVF) for producing transferable blastocysts, especially in combination with cryopreserved oocytes, when the IVF system does not work sufficiently. The present study was conducted to directly compare the efficacy of producing bovine blastocysts by ICSI and IVF from vitrified-warmed and fresh oocytes. Denuded oocytes with a detectable first polar body were vitrified-warmed using a nylon mesh device. In the non-vitrified control group, blastocyst yields 8 days after IVF and ICSI were 32.0 and 26.8%, respectively. Oocyte vitrification and subsequent IVF resulted in an impaired blastocyst yield (15.0%); however, such a loss of efficacy due to vitrification was not observed in the ICSI group (blastocyst yield, 25.2%). The alignment of cortical granules beneath the oolemma was comparable between the fresh control and vitrified-warmed oocytes. Here, we report the high survival of vitrified-warmed bovine oocytes, as assessed by ICSI.

DNA methylation and gene expression changes in mouse pre- and post-implantation embryos generated by intracytoplasmic sperm injection with artificial oocyte activation

BackgroundThe application of artificial oocyte activation (AOA) after intracytoplasmic sperm injection (ICSI) is successful in mitigating fertilization failure problems in assisted reproductive technology (ART). Nevertheless, there is no relevant study to investigate whether AOA procedures increase developmental risk by disturbing subsequent gene expression at different embryonic development stages.MethodsWe used a mouse model to explore the influence of AOA treatment on pre- and post-implantation events. Firstly, the developmental potential of embryos with or without AOA treatment were assessed by the rates of fertilization and blastocyst formation. Secondly, transcriptome high-throughput sequencing was performed among the three groups (ICSI, ICSI-AOA and dICSI-AOA groups). The hierarchical clustering and Principal Component Analysis (PCA) analysis were used. Subsequently, Igf2r/Airn methylation analysis were detected using methylation-specific PCR sequencing following bisulfite treatment. Finally, birth rate and birth weight were examined following mouse embryo transfer.ResultsThe rates of fertilization and blastocyst formation were significantly lower in oocyte activation-deficient sperm injection group (dICSI group) when compared with the ICSI group (30.8 % vs. 84.4 %, 10.0 % vs. 41.5 %). There were 133 differentially expressed genes (DEGs) between the ICSI-AOA group and ICSI group, and 266 DEGs between the dICSI-AOA group and ICSI group. In addition, the imprinted gene, Igf2r is up regulated in AOA treatment group compared to control group. The Igf2r/Airn imprinted expression model demonstrates that AOA treatment stimulates maternal allele-specific mehtylation spreads at differentially methylated region 2, followed by the initiation of paternal imprinted Airn long non-coding (lnc) RNA, resulting in the up regulated expression of Igf2r. Furthermore, the birth weight of newborn mice originating from AOA group was significantly lower compared to that of ICSI group. The pups born following AOA treatment did not show any other abnormalities during early development. All offspring mated successfully with fertile controls.ConclusionsAOA treatment affects imprinted gene Igf2r expression and mehtylation states in mouse pre- and post-implantation embryo, which is regulated by the imprinted Airn. Nevertheless, no significant differences were found in post-natal growth of the pups in the present study. It is hoped that this study could provide valuable insights of AOA technology in assisted reproduction biology.

The effect of rapid and delayed insemination on reproductive outcome in conventional insemination and intracytoplasmic sperm injection in vitro fertilization cycles.

The precise timing of insemination after oocyte retrieval is sometimes challenging. In this study, we have assessed the effect of the variation in insemination timing on reproductive outcome for both conventional insemination (CI) and intracytoplasmic sperm injection (ICSI) cycles. A single-center retrospective cohort data analysis was performed on 6559 patients (9575 oocyte retrievals) from January 2017 to July 2019. The main outcome measured was live birth rates. Secondary outcomes included fertilization rate per all oocytes retrieved, blastocyst utilization, clinical pregnancy, and miscarriage rates. The time interval between oocyte retrieval and insemination was analyzed in eight categories: 0 (0- < 0.5h), 1 (0.5- < 1.5h), 2 (1.5- < 2.5h), 3 (2.5- < 3.5h), 4 (3.5- < 4.5), 5 (4.5- < 5.5), 6 (5.5-6.5), and 7 (6.5- < 8h). The number of retrievals in each group (0-7) was 586, 1594, 1644, 1796, 1836, 1351, 641, and 127 respectively. The mean fertilization rate for CI ranged from 54.1 to 64.9% with a significant difference between time categories 0 and 5 (p < 0.001) and 1 and 5 (p < 0.0.001). The mean fertilization rate for ICSI ranged from 52.8 to 67.3% with no significant difference between time categories. Blastocyst rate for CI and ICSI was not significantly different. Miscarriage and clinical pregnancy rates in CI and ICSI were not significantly different. Live birth rates differed significantly (p < 0.05) in CI with time categories 0 and 7 representing the lowest rates, but not in the ICSI group. If performing CI or ICSI before 1.5h and > 6.5h, any detrimental effects are moderate on fertilization but do not affect blastocyst usage and birth rates. Institutional Review Board Approval from the Beth Israel Deaconess Medical Centre [IRB Protocol #: 2015P000122].

Sperm DNA fragmentation index and cumulative live birth rate in a cohort of 2,713 couples undergoing assisted reproduction treatment

To study how the choice of the first assisted reproductive technology treatment type affects the cumulative live birth rate (CLBR) in couples with high sperm DNA fragmentation index (DFI). Longitudinal cohort study. University-affiliated fertility clinic. A total of 2,713 infertile couples who underwent assisted reproductive technology treatment between 2007 and 2017 were included in the study. All invitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments (up to three fresh treatments and all associated frozen-thawed embryo transfers) offered to the couples by the public health care system were included, in total 5,422 cycles. None. The primary outcome was the CLBR. The secondary outcomes were the fertilization rate and the miscarriage rate. The IVF and ICSI groups were defined according to the method applied in the first treatment cycle. In the IVF group, the CLBR values were higher for couples with normal DFI compared with those for couples with high DFI (≥20%) (48.1% vs. 41.6% for conservative CLBR estimate and 55.6% vs. 51.4% for optimal CLBR estimate after adjustment for female age, respectively). No DFI-dependent difference was seen in the ICSI group. Our results demonstrated that a high DFI predicts a statistically significantly lower CLBR if IVF and not ICSI is applied in the first cycle of assisted reproduction.

A Novel Assisted Oocyte Activation Method Improves Fertilization in Patients With Recurrent Fertilization Failure.

Total fertilization failure (TFF) occurs in 1–3% of total intracytoplasmic sperm injection (ICSI) cycles and can reoccur in subsequent cycles. Despite the high success rate with the application of assisted oocyte activation (AOA), there is still a small number of couples who cannot obtain fertilized eggs after conventional calcium (Ca2+) ionophores-based ICSI-AOA. Six couples experiencing repeated TFF or low fertilization (<10%) after ICSI and conventional ICSI-AOA were enrolled in this study. Compared with the regular ICSI group and the conventional ICSI-AOA group, the new AOA method, a combination of cycloheximide (CHX) and ionomycin, can significantly increase the fertilization rate from less than 10 up to approximately 50% in most cases. The normal distribution of sperm-related oocyte activation factor phospholipase C zeta (PLCζ1) in the sperms of the cases indicated the absence of an aberrant Ca2+ signaling activation. The results of the whole-embryo aneuploidies analysis indicated that oocytes receiving the novel AOA treatment had the potential to develop into blastocysts with normal karyotypes. Our data demonstrated that CHX combined with ionomycin was able to effectively improve the fertilization rate in the majority of patients suffering from TFF. This novel AOA method had a potential therapeutic effect on those couples experiencing TFF, even after conventional AOA, which may surmount the severe fertilization deficiencies in patients with a repeated low fertilization or TFF.

Modified strict sperm morphology threshold aids in the clinical selection of conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).

For infertility treatment, the selection of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is decided by multiplying indicators (including fallopian tube factors, semen count, and semen motility), except for sperm morphology. In this study, we conducted a retrospective analysis, from implantation to birth, over a period of 5 years. A total of 1873 couples with primary or secondary fallopian tube factors and an increased defective sperm morphology rate (DSMR) were divided into different groups to receive IVF or ICSI cycles. By comparing the outcomes, we found that the F1 group (DSMR <96%, IVF group 1) had higher cleavage rate, biochemical pregnancy rate, clinical pregnancy rate, and live birth rate than the F3 group (DSMR >98%, IVF group 3; P < 0.05). In contrast, there was no significant difference in the ICSI subgroups. Furthermore, a comparison of the outcomes between IVF and ICSI showed that the S3 group (DSMR >98%, ICSI group 3) had higher cleavage rate (P < 0.001), biochemical pregnancy rate (P < 0.05), clinical pregnancy rate (P < 0.05) and live birth rate (P < 0.05) than the F3 group. However, the ICSI subgroup had a lower two pronuclei fertilization rate than the IVF subgroup (P < 0.05). Our data suggest that the sperm morphology should also be considered when selecting IVF or ICSI combined with other semen parameters before the first assisted reproductive technologies (ART) cycle, especially for males with severe sperm defects.

Obstetrical and Neonatal Outcomes of 3,028 Singletons Born After Advanced ART Techniques: Ejaculated Sperm Intracytoplasmic Sperm Injection, Artificial Oocyte Activation, in Vitro Maturation and Testicular Sperm Extraction

Background: To evaluate obstetrical and neonatal outcomes of singletons conceived after advanced assisted reproductive technology (ART) techniques: conventional IVF pregnancies (C-IVF), ejaculated sperm intracytoplasmic sperm injection (ICSI), assisted oocyte activation (AOA), in vitro maturation (IVM), and testicular sperm extraction (TESE). Methods: The subjects were 3,028 singletons who were born after fresh or frozen embryo transfer. The subjects were separated into five groups: C-IVF ([Formula: see text]), ICSI ([Formula: see text]), AOA ([Formula: see text]), IVM ([Formula: see text]), and TESE ([Formula: see text]). We evaluated obstetrical and neonatal outcomes calculating the adjusted odds ratio (AOR) using multivariable logistic regression analyses for fresh and frozen embryos and for cleavage and blastocyst transfer. The C-IVF group was used as a background control for the ICSI group. Moreover, the TESE, AOA, and IVM groups were compared to the ICSI group to evaluate the effects of the ICSI procedure itself. Results: The incidence of perinatal complications was significantly lower in the ICSI-fresh group ([Formula: see text], 95% CI: 0.10–0.83, [Formula: see text]). Regarding sex ratio, the IVM was significantly associated with sex ratio imbalance toward female in both fresh and frozen groups ([Formula: see text], 95% CI: 0.10–0.96, [Formula: see text], 95% CI: 0.07–0.98, [Formula: see text]). On the other hand, there were no significant differences in preterm birth rate, low birth weight rate and congenital abnormalities rate between conventional IVF, ICSI, and the other groups. Conclusions: There were no negative effects on obstetrical and neonatal outcomes between conventional IVF and ICSI. Although this was a limited sample size study, advanced ART technologies such as AOA, IVM, and TESE also seem to have a low risk of adverse impact on obstetrical and neonatal outcomes but may have a slight impact on sex ratio.

Intracytoplasmic sperm injection versus conventional in-vitro fertilisation in couples with infertility in whom the male partner has normal total sperm count and motility: an open-label, randomised controlled trial

The use of intracytoplasmic sperm injection has increased substantially worldwide, primarily in couples with non-male factor infertility. However, there is a paucity of evidence from randomised trials supporting this approach compared with conventional in-vitro fertilisation (IVF). We aimed to investigate whether intracytoplasmic sperm injection would result in a higher livebirth rate compared with conventional IVF. This open-label, multicentre, randomised trial was done at two IVF centres in Ho Chi Minh City, Vietnam (IVFMD, My Duc Hospital and IVFAS, An Sinh Hospital). Eligible couples were aged at least 18 years and the male partner's sperm count and motility (progressive motility) were normal based on WHO 2010 criteria. Couples had to have undergone two or fewer previous conventional IVF or intracytoplasmic sperm injection attempts, have used an antagonist protocol for ovarian stimulation, and agree to have two or fewer embryos transferred. Couples were randomly assigned (1:1) to undergo either intracytoplasmic sperm injection or conventional IVF, using block randomisation with variable block size of 2, 4, or 8 and a telephone-based central randomisation method. The computer-generated randomisation list was prepared by an independent statistician who had no other involvement in the study. Embryologists and couples were not masked to study groups because of the type of interventions and differences in hospital fees, but clinicians performing embryo transfer were unaware of study group allocation. The primary outcome was livebirth after the first embryo transfer from the initiated cycle. Analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT03428919. Between March 16, 2018, and Aug 12, 2019, we randomly assigned 1064 couples to intracytoplasmic sperm injection (n=532) or conventional IVF (n=532). Livebirth after the first embryo transfer from the initiated cycle occurred in 184 (35%) of 532 couples randomly assigned to intracytoplasmic sperm injection and in 166 (31%) of 532 couples randomly assigned to conventional IVF (absolute difference 3·4%, 95% CI -2·4 to 9·2; risk ratio [RR] 1·11, 95% CI 0·93 to 1·32; p=0·27). 29 (5%) couples in the intracytoplasmic sperm injection group and 34 (6%) couples in the conventional IVF group had fertilisation failure (absolute difference -0·9%, -4·0 to 2·1, RR 0·85, 95% CI 0·53 to 1·38; p=0·60). In couples with infertility in whom the male partner has a normal total sperm count and motility, intracytoplasmic sperm injection did not improve the livebirth rate compared with conventional IVF. Our results challenge the value of the routine use of intracytoplasmic sperm injection in assisted reproduction techniques for this population. My Duc Hospital and Merck Sharp and Dohme.

ICSI Does Not Improve Live Birth Rates but Yields Higher Cancellation Rates Than Conventional IVF in Unexplained Infertility.

Objectives: Unexplained infertility has been one of the indications for utilization of intracytoplasmic sperm injection (ICSI). However, whether ICSI should be preferred to IVF for patients with unexplained infertility remains an open question. This study aims to determine if ICSI improves the clinical outcomes over conventional in vitro fertilization (IVF) in couples with unexplained infertility.Methods: This was a retrospective cohort study of 549 IVF and 241 ICSI cycles for patients with unexplained infertility at a fertility center of a university hospital from January 2016 and December 2018. The live birth rate and clinical pregnancy rate were compared between the two groups. Other outcome measures included the implantation rate, miscarriage rate, and fertilization rate.Results: The live birth rate was 35.2% (172/488) in the IVF group and 33.3% (65/195) in ICSI group, P = 0.635. The two groups also had similar clinical pregnancy rates, implantation rates, and miscarriage rates. The fertilization rate of IVF group was significantly higher than that of ICSI group (53.8 vs. 45.7%, P = 0.000, respectively). Sixty-one and 46 patients did not transfer fresh embryos in IVF and ICSI cycles, respectively. Patients with IVF cycles had lower cancellation rates than those with ICSI (11.1 vs. 19.1%, P = 0.003, respectively).Conclusion: ICSI does not improve live birth rates but yields higher cancellation rates than conventional IVF in the treatment of unexplained infertility.

Comparison of physiological-ICSI (PICSI) with ICSI in cases of moderate to severe oligoasthenoteratozoospermia (OAT) − a randomized control study

Objective: To compare the efficiency of physiological intracytoplasmic sperm injection (PICSI) over intracytoplasmic sperm injection (ICSI) in Oligoasthenoteratozoospermic patients. Design: Randomized control study. Setting: KJIVF and laparoscopy center Delhi. Methods: From September 2019 to May 2020, 45 patients of male factor felled under our criteria of OAT were divided into two groups of PICSI and ICSI. Sperm selection was performed under high magnification in both the groups and results were compared. Outcome measure: Primary outcome: Fertilization rate, cleavage rate, blastulation, and utility rate; Secondary outcome: Clinical pregnancy rates and miscarriage rates. Results: 20 PICSI and 25 ICSI treatments were performed and observed that the rate of blastulation and embryo utility shows significant difference in PICSI group (P = 0.013). The pregnancy percentage was also better in PICSI but implantation, fertilization, cleavage; clinical pregnancy rates were clinically comparable in both the groups but not statistically significant. Conclusion: The outcomes of our study are independent of male factor and it only depends on intervention whether it was PICSI or ICSI. The blastulation rate and embryo utility shows statistically significant difference between PICSI and ICSI groups. Hence, we are slowly progressing toward the superiority of PICSI over ICSI but enough evidences are still not available.

Comparison of physiological-ICSI (PICSI) with ICSI in cases of moderate to severe oligoasthenoteratozoospermia (OAT) − a randomized control study

Objective: To compare the efficiency of physiological intracytoplasmic sperm injection (PICSI) over intracytoplasmic sperm injection (ICSI) in Oligoasthenoteratozoospermic patients. Design: Randomized control study. Setting: KJIVF and laparoscopy center Delhi. Methods: From September 2019 to May 2020, 45 patients of male factor felled under our criteria of OAT were divided into two groups of PICSI and ICSI. Sperm selection was performed under high magnification in both the groups and results were compared. Outcome measure: Primary outcome: Fertilization rate, cleavage rate, blastulation, and utility rate; Secondary outcome: Clinical pregnancy rates and miscarriage rates. Results: 20 PICSI and 25 ICSI treatments were performed and observed that the rate of blastulation and embryo utility shows significant difference in PICSI group (P = 0.013). The pregnancy percentage was also better in PICSI but implantation, fertilization, cleavage; clinical pregnancy rates were clinically comparable in both the groups but not statistically significant. Conclusion: The outcomes of our study are independent of male factor and it only depends on intervention whether it was PICSI or ICSI. The blastulation rate and embryo utility shows statistically significant difference between PICSI and ICSI groups. Hence, we are slowly progressing toward the superiority of PICSI over ICSI but enough evidences are still not available.

Concentrations of the endocannabinoid N-arachidonoylethanolamine in the follicular fluid of women with endometriosis: the role of M1 polarised macrophages.

Although N-arachidonoylethanolamine (AEA; also known as anandamide) is present in human follicular fluid (FF), its regulation remains unknown. Therefore, the aims of the present study were to: (1) investigate the relationships between FF AEA concentrations in women undergoing assisted reproductive technology and their age, body mass index, ART characteristics and fertility treatment outcomes; and (2) assess how different inflammatory patterns may trigger AEA production by human granulosa cells (hGCs). FF AEA concentrations were higher in women undergoing IVF than in those undergoing intracytoplasmic sperm injection group. FF AEA median concentrations were lower in women undergoing ART because of male factor infertility than in women with endometriosis (1.6 vs 2.5nM respectively), but not women with tubal, hormonal or unexplained infertility (1.6, 2.4 and 1.9nM respectively). To evaluate the effects of macrophages on AEA production by hGCs, hGCs were cocultured with monocyte-derived macrophages. The conditioned medium from M1 polarised macrophages increased AEA production by hGCs. This was accompanied by an increase in AEA-metabolising enzymes, particularly N-acyl phosphatidylethanolamine-specific phospholipase D. The results of the present study show that high FF AEA concentrations in patients with endometriosis may be associated with the recruitment of inflammatory chemokines within the ovary, which together may contribute to the decreased reproductive potential of women with endometriosis. Collectively, these findings add a new player to the hormone and cytokine networks that regulate fertility in women.

Assessing the cognitive and behavioral development of 3-year-old children born from fathers with severe male infertility

Despite the large number of babies born worldwide following intracytoplasmic sperm injection, concerns about the procedure's safety still exist owing to the use of suboptimal spermatozoa. Thus, follow-up of children conceived via intracytoplasmic sperm injection is highly recommended. We propose the use of parent-administered questionnaires to monitor the development of offspring conceived via intracytoplasmic sperm injection. This study aimed to determine whether male infertility treatment affects offspring development. We compared obstetrical and neonatal outcomes andphysical and psychological development of toddlers conceived viainvitro fertilization and intracytoplasmic sperm injection. Once newborns reached 3 years of age, participating patients were sent a set of parent-administered questionnaires, including the Ages and Stages Questionnaires; Prescreening Developmental Questionnaire 2; Peabody Developmental Motor Scales, Second Edition; Social Skills Rating System; Parenting Stress Index, Third Edition; and Child Behavior Checklist for Ages 2-3. Child development was measured by the Ages and Stages Questionnaires; Prescreening Developmental Questionnaire 2; and Peabody Developmental Motor Scales, Second Edition, questionnaires, whereas Social Skills Rating System; Parenting Stress Index, Third Edition; and Child Behavior Checklist for Ages 2-3 questionnaires were used to measure child behavior. The child's developmental or behavioral outcome was considered "abnormal" when he or she scored below average in ≥2 questionnaires from the respective category. We also conducted subanalyses to assess the effects of male genomic integrity, DNA fragmentation, chemical exposure, utilization of surgically retrieved spermatozoa, and extended embryo culture to determine the development of a child conceived via intracytoplasmic sperm injection. A total of 12,306 couples met the inclusion criteria for this study; 1914 of 7433 patients (25.8%) who underwent intracytoplasmic sperm injection and 451 of 4873 patients (9.3%) who underwent invitro fertilization returned the questionnaires. Our comparison of obstetrical outcomes between the 2 groups did not reveal any significant differences in the mode of delivery distribution, with most mothers having uncomplicated vaginal deliveries. Furthermore, gender distribution, gestational ages, and birthweights were also comparable between children conceived via intracytoplasmic sperm injection and invitro fertilization. However, children conceived via invitro fertilization displayed impaired developmental characteristics compared with the intracytoplasmic sperm injection-conceived cohort (adjusted odds ratio, 0.72; 95% confidence interval, 0.5-0.9; P=.0004). There was no difference in child behavior. Furthermore, 3 cases of autism were reported, 1 case from the invitro fertilization group and 2 from the intracytoplasmic sperm injection group, all conceived from couples with an older male partner. Ages and Stages Questionnaires outcomes were also compared for the offspring conceived via invitro fertilization and intracytoplasmic sperm injection by gender; however, no significant differences were observed. In addition, 5 separate subanalyses were then conducted exclusively for the intracytoplasmic sperm injection-conceived group. Levels of spermatogenic failure, DNA fragmentation, and chemical exposure did not significantly affect offspring development. Interestingly, although the length of embryo culture did not seem to influence child development, the abnormal behavior rate was significantly higher in children from the day 3 embryo transfer cohort (adjusted odds ratio, 0.4; 95% confidence interval, 0.05-0.34; P=.04). Children conceived via intracytoplasmic sperm injection from ejaculated spermatozoa displayed impaired developmental and behavioral characteristics compared with toddlers conceived from surgically retrieved specimens (adjusted odds ratio, 4.9; 95% confidence interval, 1.2-20.7; P=.05). Most children conceived via intracytoplasmic sperm injection and invitro fertilization are developing well without significant delays. Although the development of a child conceived via intracytoplasmic sperm injection was not affected by most of the variables assessed, those conceived from surgically retrieved spermatozoa were at a considerably lower risk of abnormal developmental and abnormal behavioral characteristics than offspring conceived from ejaculated specimens. However, given the small numbers of respondents available for many subgroups of interest, further studies of outcomes of children born from fathers with severe male factor infertility are warranted.

A New Day 4 Grading System to Assess Embryo Quality in Frozen Embryo Transfer Cycles

To present a new day 4 (D4) embryo grading system to assess embryos in frozen-thawed embryo transfer (FET) cycles. A new grading system (grades A-E) was developed from the 2011 ESHRE Istanbul Consensus for D4 embryos in FET cycles. Embryos with complete compaction were classified as grade A; those with partial compaction were assigned as grade B; and those without compaction were classified as grades C, D, and E according to their different blastomere number ratio (BNR; number of embryo blastomeres on D4/number of embryo blastomeres on D3, D4/D3). Embryos with a BNR of ≥ 1.5 were defined as grade C, those with a BNR of ≥ 1.2 and < 1.5 were defined as grade D, and those with a BNR of ≥ 1.0 and < 1.2 were defined as grade E. Using this proposed grading model, 5460 embryos with known implantation data were retrospectively analyzed after D4 transfer in FET cycles. The transferred embryos exhibited a similar declining trend in implantation and live birth rates from the top grade A to the lowest grade E. The in vitro fertilization group showed increased implantation rates of grade B and E embryos compared with the intracytoplasmic sperm injection group (grade B: 41.99%, 34.63%, χ2 = 5.84, p < 0.05 and grade E: 18.98%, 14.08, χ2 = 75.62, p < 0.01). Receiver-operating characteristic analysis revealed that our proposed model predicted the implantation outcomes and live birth rates of all embryos (area under the curve = 0.65; 95% confidence interval [CI],0.63-0.66; p < 0.01 and AUC = 0.73; 95%CI, 0.65-0.84; p < 0.001, respectively). This study demonstrates that the new grading system provided by us can be a useful tool for assisting embryo selection via changes in embryo morphology. D4 embryo transfer provides a simple and applicable method for FET cycles in daily practice.

The effect of ICSI in infertility couples with non-male factor: a systematic review and meta-analysis.

We performed a systematic review and meta-analysis of available literature to investigate the efficacy of the intracytoplasmic sperm injection (ICSI) in couples with non-male factor with respect to the clinical outcomes. The literature search was based on EMBASE, PubMed, and the Cochrane Library. All studies published after 1992 until February 2020 and written in English addressing patients in the presence of normal semen parameters subjected to ICSI and in vitro fertilization (IVF) were eligible. Reference lists of retrieved articles were hand-searched for additional studies. The primary outcomes were fertilization rate, clinical pregnancy rate, and implantation rate; the secondary outcomes were good-quality embryo rate, miscarriage rate, and live birth rate. Four RCTs and twenty-two cohort studies fulfilling the inclusion criteria were included. Collectively, a meta-analysis of the outcomes in RCTs showed that compared to IVF, ICSI has no obvious advantage in fertilization rate (RR = 1.16, 95% CI: 0.83-1.62), clinical pregnancy rate (RR = 1.04, 95% CI: 0.66-1.64), implantation rate (RR = 1.12, 95% CI: 0.67-1.86), and live birth rate (RR = 1.17, 95% CI: 0.43-3.15). Pooled results of cohort studies demonstrated a statistically significant higher fertilization rate (RR = 1.16, 95% CI: 1.03-1.31) and miscarriage rate (RR = 1.04, 95% CI: 1.01-1.06) in the ICSI group; furthermore, higher clinical pregnancy rate (RR = 0.85, 95% CI: 0.77-0.94), implantation rate (RR = 0.78, 95% CI: 0.65-0.95), and live birth rate (RR = 0.86, 95% CI: 0.79-0.94) was founded in the IVF group; no statistically significant difference was observed in good-quality embryo rate (RR = 0.98, 95% CI: 0.93-1.04). ICSI has no obvious advantage in patients with normal semen parameters. Enough information is still not available to prove the efficacy of ICSI in couples with non-male factor infertility comparing to IVF.

Associations between a new day 4 embryo grading system and implantation rates in frozen embryo transfer (FET) cycles.

The purpose of this study is to present a new day 4 (D4) embryo grading system for the assessment of embryos in frozen-thawed embryo transfer (FET) cycles.A new grading system (grades A–E) was modified from the 2011 ESHRE Istanbul Consensus for D4 embryos in FET cycles. In total, we retrospectively analyzed 5640 embryos with known implantation data after D4 transfer in FET cycles by using this proposed grading model.The transferred embryos exhibited a similar declining trend in implantation rates from the top grade A to the lowest grade E. The implantation rates of grade B and E embryos in the in vitro fertilization group were significantly higher than that in the intracytoplasmic sperm injection group (grade B: 41.82%, 35.23%, χ2 = 5.85, P < .05 and grade E: 18.53%, 14.81, χ2 = 76.86, P < .01, respectively). The receiver operating characteristic analysis showed that our proposed model predicted the implantation outcomes of all embryos (area under the ROC curve = 0.65; 95% CI, 0.63–0.66; P < .01).This study demonstrated that the new grading system provided by us turned out to be a useful tool in assisting embryo selection via embryo morphological changes, and D4 embryo transfer provided a simple and applicable method for a daily routine in FET cycles.

The impaired development of sheep ICSI derived embryos is not related to centriole dysfunction

While intracytoplasmic sperm injection (ICSI) is an asset in human Assisted Reproduction Technologies (ART), its outcomes, in terms of blastocyst, is still unacceptably low in ruminants. The picture typically found in ICSI derived bovine and ovine embryos is an asymmetry between a high activation rate, marked by a pronuclear development, and a low first cleavage rate. Abnormal centriole function has been indicated as a possible factor which undermines embryonic development following ICSI, especially when Freeze Dried spermatozoa (FD) are used. In order to verify the hypothesis that centriole dysfunction might be responsible for low ICSI outcomes in sheep, we have investigated micro-tubular dynamics, markedly aster nucleation, in fertilized sheep zygotes by ICSI with frozen/thawed (FT) and FD spermatozoa; In Vitro Fertilized (IVF) sheep oocytes were used as control. The spermatozoa aster nucleation was assessed at different time points following ICSI and IVF by immune-detection of α-tubulin. Pronuclear stage, syngamy and embryo development were assessed. No difference was noticed in the timing of aster nucleation and microtubule elongation in ICSI-FT derived embryos with control IVF ones, while a delay was recorded in ICSI-FD ones. The proportion of 2-pronuclear stage zygotes was similar in ICSI-FT and ICSI-FD (47% and 53%, respectively), both much lower comparing the IVF ones (73%). Likewise, syngamy was observed in a minority of both ICSI groups (28.5% vs 12.5% in ICSI-FT/FD respectively) comparing to IVF controls (50%), with a high number of zygotes blocked at the 2-pronuclear stage (71.5% vs 87.5% respectively). While no significant differences were noticed in the cleavage rate between ICSI-FD, ICSI-FT and IVF groups (31%, 34% and 44%) respectively, development to blastocyst stage was markedly compromised in both ICSI groups, especially with FD spermatozoa (10% in ICIS-FD and 19% in ICSI-FT vs 33% in IVF (P < 0.005, ICSI-FD vs IVF and P < 0.05, IVF vs ICSI-FT, respectively). Hence, here we have demonstrated that the reduced cleavage, and the ensuing impaired development to blastocysts stage of ICSI derived sheep embryos is not related to centriole dysfunction, as suggested by other authors. The major recorded problem is the lack of syngamy in ICSI derived zygotes, an issue that should be addressed in further studies to improve ICSI procedure in sheep embryos.