Limited clinical information is available regarding sperm population parameters that are important for use with equine intracytoplasmic sperm injection (ICSI). Therefore, the appropriateness of a sample of sperm is typically not known before ICSI. The aim of our study was to determine which sperm population characteristics were predictive of ICSI outcome. Frozen-thawed sperm samples (n = 114) from 37 stallions in a clinical program were analyzed after ICSI for percentages of normal morphology (MORPH+), live as assessed by eosin/nigrosin stain (LIVE+), membrane intact as assessed by hypoosmotic swelling test (HOS+), and DNA fragmentation determined by sperm chromatin dispersion (DNA-). ICSI was performed on 147 oocytes, and cleavage (≥2 cells), embryo development (morula or blastocyst), and pregnancy status after embryo transfer were determined. Among the examined sperm parameters, LIVE + correlated positively with MORPH+ and HOS+, and MORPH + negatively with DNA-; no other significant correlations were observed. When used for ICSI, sperm population percentages for MORPH+ and DNA- were not predictive of ICSI outcome, including cleavage, embryo development, and establishment of a pregnancy. Sperm population percentages significantly affecting ICSI outcomes were LIVE+ and HOS + for oocyte cleavage, LIVE + for embryo development, and HOS + for establishment of a pregnancy. The probability of a pregnancy was significantly higher for sperm populations having HOS+ ≥40% than populations having HOS+ ≤20%. The mean age of the donor mare per sperm-injected oocyte did not differ for oocyte cleavage, embryo production, or establishment of pregnancy. In our study, the probability of sperm-injected oocytes to develop into an embryo (morula or blastocyst) improved when sperm were selected from a population with higher indicators of membrane integrity (LIVE+ and HOS+).

The current treatment regimen for ovarian stimulation in Intracytoplasmic sperm injection (ICSI) patients is daily injections of Gonadotropins. Recombinant DNA technologies have produced a new recombinant molecule that is a long-acting Follicle Stimulating Hormone (FSH), named corifollitropin alfa. A single injection of long-acting FSH can replace seven daily FSH injections during the first week of controlled ovarian stimulation (COS) and can make assisted reproduction more patients-friendly. There is limited data with different results in this area.

Objectives: To investigate the differences in clinical pregnancy, miscarriage, and live birth rates when male partners were diagnosed with a varicocele and to compare these outcomes to those without and study the outcomes based on the grade of varicocele. Methods: The retrospective study was based on a cohort of consecutive infertile couples undergoing assisted reproductive technology (ART) at the Reproductive Center of Shandong Provincial Hospital affiliated to the Shandong University during the period between January 2017 and December 2018. A total of 4203 couples comprised of men with and without varicocele undergoing the first ART cycle (1501 intrauterine inseminations (IUI), 1623 in vitro fertilisations (IVF) and 1079 intracytoplasmic sperm injections (ICSI)) were included. Semen parameters and ART outcomes were determined. Results: ICSI (26.5%) originated from men with a significant lower level in sperm concentration and motility but with a strict normal morphology had a higher prevalence of varicocele than men undergoing IUI (20.7%) and IVF (18.1%). In IUI, the odds ratios (ORs) for pregnancy and live birth were significantly lower for couples in men diagnosed with grades 1 or 2 varicocele as compared to those for men with grade 3 varicocele. In IVF, ORs for live birth where men were diagnosed with grades 1 or 2 varicocele were also lower than those for men with grade 3,whereas a higher miscarriage rate was found when men had grades 1 or 2 varicocele than when men had grade 3. However, for ICSI, no significant outcomes were found in grades 1, 2 or 3 varicocele versus the no varicocele group. Conclusions: The increasing grade of varicocele was negatively associated with sperm parameters and can alter the outcome of further IUI/IVF.

Various luteal phase supports (LPSs) have been proven to increase the pregnancy rate in fresh cycles of in vitro fertilization or intracytoplasmic sperm injection; however, there is still significant debate regarding the optimal use of LPS.

Sperm malformation is a direct factor for male infertility. Multiple morphological abnormalities of the flagella (MMAF), a severe form of asthenoteratozoospermia, are characterized by immotile spermatozoa with malformed and/or absent flagella in the ejaculate. Previous studies indicated genetic heterogeneity in MMAF. To further define genetic factors underlying MMAF, we performed whole-exome sequencing in a cohort of 90 Chinese MMAF-affected men. Two cases (2.2%) were identified as carrying bi-allelic missense DNAH8 variants, variants which were either absent or rare in the control human population and were predicted to be deleterious by multiple bioinformatic tools. Re-analysis of exome data from a second cohort of 167 MMAF-affected men from France, Iran, and North Africa permitted the identification of an additional male carrying a DNAH8 homozygous frameshift variant. DNAH8 encodes a dynein axonemal heavy-chain component that is expressed preferentially in the testis. Hematoxylin-eosin staining and electron microscopy analyses of the spermatozoa from men harboring bi-allelic DNAH8 variants showed a highly aberrant morphology and ultrastructure of the sperm flagella. Immunofluorescence assays performed on the spermatozoa from men harboring bi-allelic DNAH8 variants revealed the absent or markedly reduced staining of DNAH8 and its associated protein DNAH17. Dnah8-knockout male mice also presented typical MMAF phenotypes and sterility. Interestingly, intracytoplasmic sperm injections using the spermatozoa from Dnah8-knockout male mice resulted in good pregnancy outcomes. Collectively, our experimental observations from humans and mice demonstrate that DNAH8 is essential for sperm flagellar formation and that bi-allelic deleterious DNAH8 variants lead to male infertility with MMAF.

This study illustrated the global contribution to assisted reproductive technologies (ARTs) research in MEDLINE database from 1998 to 2014.

Compare the efficacy of surrogate or gestational carrier (GC) cycles to that of autologous in vitro fertilization (IVF)/intracytoplasmic sperm injections (ICSI) in patients with gynecologic or medical co-morbidities contraindicative to pregnancy.

Many azoospermic men do not possess mature spermatozoa at the time of surgical sperm extraction. This study is a systematic review and meta-analysis evaluating outcomes following round spermatid injection (ROSI), a technique which utilizes immature precursors of spermatozoa for fertilization. An electronic search was performed to identify relevant articles published through October 2018. Human cohort studies in English involving male patients who had round spermatids identified and used for fertilization with human oocytes were included. Fertilization rate, pregnancy rate, and resultant delivery rate were assessed following ROSI. Meta-analysis outcomes were analyzed using a random-effects model. Data were extracted from 22 studies involving 1099 couples and 4218 embryo transfers. The fertilization rate after ROSI was 38.7% (95% confidence interval [CI]: 31.5%-46.3%), while the pregnancy rate was 3.7% (95% CI: 3.2%-4.4%). The resultant delivery rate was low, with 4.3% of embryo transfers resulting in a delivery (95% CI: 2.3%-7.7%). The pregnancy rate per couple was 13.4% (95% CI: 6.8%-19.1%) and the resultant delivery rate per couple was 8.1% (95% CI: 6.1%-14.4%). ROSI has resulted in clinical pregnancies and live births, but success rates are considerably lower than those achieved with mature spermatozoa. While this technique may be a feasible alternative for men with azoospermia who decline other options, couples should be aware that the odds of a successful delivery are greatly diminished and the prognosis is relatively poor.

This analysis was performed to evaluate the effects of intrauterine injection of human chorionic gonadotropin (hCG) before fresh embryo transfer (ET) on the outcomes of in vitro fertilization and intracytoplasmic sperm injection.

Women submitted to ART treatments represent a select subgroup of individuals. Several studies have described the relationship between TAI and pregnancy outcomes as a result of ART, with contradictory results. The purpose of this systematic review was to determine the association between TAI and the risk of miscarriage in pregnancies resulting from ART. MEDLINE via PubMed, LILACS and Embase were searched for studies published in peer-reviewed journals from 1999 to 2017. The studies were summarized using the fixed effects model and the Peto's method to calculate RR in order to flesh out the association between TAI and spontaneous abortion. Only four papers were included in this systematic review and meta-analysis. Thirty-one miscarriages were observed in 210 clinical pregnancies of women with antithyroid antibodies; and 158 miscarriages were seen in 1,371 pregnancies without antithyroid antibodies. The meta-analysis failed to find an association between TAI and higher risk of reproductive loss, RR=0.94 95% confidence interval: 0.71-1.24; p=0.879. In conclusion, the presence of antithyroid antibodies was not associated with increased reproductive loss in patients submitted to ART treatments. It is our opinion that the presence of antithyroid antibodies should be considered as a secondary biomarker of autoimmune disease, rather than an actual cause of miscarriage in patients undergoing ART. Due to the small amount of evidence on the matter, the determination of TAI before the initiation of ART should be limited to research contexts.

Male infertility is a multifactorial disease with a strong genetic background. Abnormal sperm morphologies have been found to be closely related to male infertility. Here, we conducted whole-exome sequencing in a cohort of 150 Han Chinese men with asthenoteratozoospermia. Two novel hemizygous mutations were identified in USP26, an X-linked gene preferentially expressed in the testis and encoding a deubiquitinating enzyme. These USP26 variants are extremely rare in human population genome databases and have been predicted to be deleterious by multiple bioinformatics tools. Hematoxylin-eosin staining and electron microscopy analyses of the spermatozoa from men harboring hemizygous USP26 variants showed a highly aberrant morphology and ultrastructure of the sperm heads and flagella. Real-time quantitative PCR and immunoblotting assays revealed obviously reduced levels of USP26 mRNA and protein in the spermatozoa from men harboring hemizygous deleterious variants of USP26. Furthermore, intracytoplasmic sperm injections performed on infertile men harboring hemizygous USP26 variants achieved satisfactory outcomes. Overall, our study demonstrates that USP26 is essential for normal sperm morphogenesis, and hemizygous USP26 mutations can induce X-linked asthenoteratozoospermia. These findings will provide effective guidance for the genetic and reproductive counseling of infertile men with asthenoteratozoospermia.

What is the evidence pertaining to availability, effectiveness and safety of ART in sub-Saharan Africa?

The perinuclear theca (PT) of the eutherian sperm head is a cytoskeletal-like structure that houses proteins involved in important cellular processes during spermiogenesis and fertilization. Building upon our novel discovery of non-nuclear histones in the bovine PT, we sought to investigate whether this PT localization was a conserved feature of eutherian sperm. Employing cell fractionation, immunodetection, mass spectrometry, qPCR, and intracytoplasmic sperm injections (ICSI), we examined the localization, developmental origin, and functional potential of histones from the murid PT. Immunodetection localized histones to the post-acrosomal sheath (PAS) and the perforatorium (PERF) of the PT but showed an absence in the sperm nucleus. MS/MS analysis of selectively extracted PT histones indicated that predominately core histones (i.e., H3, H3.3, H2B, H2A, H2AX, and H4) populate the murid PT. These core histones appear to be de novo-synthesized in round spermatids and assembled via the manchette during spermatid elongation. Mouse ICSI results suggest that early embryonic development is delayed in the absence of PT-derived core histones. Here, we provide evidence that core histones are de novo-synthesized prior to PT assembly and deposited in PT sub-compartments for subsequent involvement in chromatin remodeling of the male pronucleus post-fertilization.

A significant portion of the research on assisted reproductive technologies explores ethical, legal, and social implications. It has an impact on social perceptions, the evolution of norms of clinical practices, regulations and public funding. This paper reviews and maps the geographical distribution to test the hypothesis of geographical concentration and classifies the output by fields and topics.

Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive disease manifested with recurrent infections of respiratory tract and infertility. DNAAF3 is identified as a novel gene associated with PCD and different mutations in DNAAF3 results in different clinical features of PCD patients, such as situs inversus, sinusitis and bronchiectasis. However, the sperm phenotypic characteristics of PCD males are generally poorly investigated. Our reproductive medicine centre received a case of PCD patient with infertility, who presented with sinusitis, recurrent infections of the lower airway and severe asthenozoospermia; However, no situs inversus was found in the patient. A novel homozygous mutation in DNAAF3(c.551T>A; p.V184E) was identified in the PCD patient by whole-exome sequencing. Subsequent Sanger sequencing further confirmed that the DNAAF3 had a homozygous missense variant in the fifth exon. Transmission electron microscopy and immunostaining analysis of the sperms from the patient showed a complete absence of outer dynein arms and partial absence of inner dynein arms, which resulted in the reduction in sperm motility. However, this infertility was overcome by intracytoplasmic sperm injections, as his wife achieved successful pregnancy. These findings showed that the PCD-associated pathogenic mutation within DNAAF3 also causes severe asthenozoospermia and male infertility ultimately due to sperm flagella axoneme defect in humans. Our study not only contributes to understand the sperm phenotypic characteristics of patients with DNAAF3 mutations but also expands the spectrum of DNAAF3 mutations and may contribute to the genetic diagnosis and therapy for infertile patient with PCD.

Thyroid autoimmunity (TAI) - the presence of anti-thyroid peroxidase and/or anti-thyroglobulin antibodies - affects 8-14% of reproductively-aged women. It is hotly debated whether TAI adversely affects IVF/ICSI outcomes. This systematic review and meta-analysis evaluated the relationship between thyroid autoimmunity (TAI) and IVF/ICSI outcomes, both overall and amongst euthyroid women of known age using strict criteria for grouping pregnancy outcomes.

As a type of severe asthenoteratospermia, multiple morphological abnormalities of the flagella (MMAF) are characterized by the presence of immotile spermatozoa with severe flagellar malformations. MMAF is a genetically heterogeneous disorder, and the known MMAF-associated genes can only account for approximately 60% of human MMAF cases. Here we conducted whole-exome sequencing and identified bi-allelic truncating mutations of the TTC29 (tetratricopeptide repeat domain 29) gene in three (3.8%) unrelated cases from a cohort of 80 MMAF-affected Han Chinese men. TTC29 is preferentially expressed in the testis, and TTC29 protein contains the tetratricopeptide repeat domains that play an important role in cilia- and flagella-associated functions. All of the men harboring TTC29 mutations presented a typical MMAF phenotype and dramatic disorganization in axonemal and/or other peri-axonemal structures. Immunofluorescence assays of spermatozoa from men harboring TTC29 mutations showed deficiency of TTC29 and remarkably reduced staining of intraflagellar-transport-complex-B-associated proteins (TTC30A and IFT52). We also generated a Ttc29-mutated mouse model through the use of CRISPR-Cas9 technology. Remarkably, Ttc29-mutated male mice also presented reduced sperm motility, abnormal flagellar ultrastructure, and male subfertility. Furthermore, intracytoplasmic sperm injections performed for Ttc29-mutated mice and men harboring TTC29 mutations consistently acquired satisfactory outcomes. Collectively, our experimental observations in humans and mice suggest that bi-allelic mutations in TTC29, as an important genetic pathogeny, can induce MMAF-related asthenoteratospermia. Our study also provided effective guidance for clinical diagnosis and assisted reproduction treatments.

Embryo morphology and morphokinetics have been studied for their association with euploid embryos. However, the results are controversial, especially in the advanced-aged women group, when the risk of aneuploidy increases significantly. This prospective cohort study evaluated the association between embryo development between day-3 cleavage and day-5 blastocyst stages and euploidy rates, determined using preimplantation genetic testing for aneuploidy (PGT-A). Embryos from women aged 35 years and above who underwent intracytoplasmic sperm injections and PGT-A were studied. Day-3 cleavage-stage embryos were evaluated for their cell number, and day-5 blastocyst-stage embryos were evaluated for their morphological grade. Embryo development from day 3 to day 5 was categorized as either good or poor development and evaluated for its association with the PGT-A results. We evaluated 325 embryos from 101 infertile couples. It was found that 55.17% of blastocysts with good development and 29.83% with poor development were euploid. A significant association was found between embryo development and euploidy rates in advanced-aged women (p < 0.001). Also, there were significantly higher rates of euploid embryos with good blastocyst morphological grades, especially blastocyst expansion grades and trophectoderm grades. In conclusion, embryo morphokinetics shows promising results in predicting euploidy in advanced female age.

The purpose of this prospective study was to compare the ovarian response and pregnancy outcomes
in the infertile women with endometrioma undergoing assisted reproductive technologies (ART) in two
groups, who were underwent laparoscopic cystectomy and received gonadotropin releasing hormone-agonist
(GnRH-agonist) and who only received GnRH-agonist without any surgery.
Materials and Methods: In this prospective clinical trial study, 79 infertile women with asymptomatic endometriomas
cyst (2-6 cm) were enrolled and randomly assigned to two groups. First group underwent laparoscopic
cystectomy and received GnRH-agonist. Second group only received GnRH-agonist without any surgery. Following
ovulation induction, all patients underwent intracytoplasmic sperm injection (ICSI). Different parameters
such as the number of retrieved oocytes and embryos; were made our outcomes that analyzed using SPSS.
Results: The pregnancy rate, chemical and clinical, and live birth rate were higher in the combined group,
although these differences were not statistically significant (48.48% vs. 30.8%, P=0.12, 36.36% vs. 25.6%,
P=0.32, 36.36% vs. 23.1%, P=0.29). The number of injections, antral follicles, retrieved oocytes, mature oocytes,
total embryos, transferred embryos and duration of stimulation were similar in two groups.
Conclusion: Laparoscopic cystectomy followed by receiving GnRH-agonist improves pregnancy outcomes in endometrioma
prior to treatment with ART (registration number: IRCT201106116689N2).

Mechanical allodynia is a major symptom of neuropathic pain whereby innocuous touch evokes severe pain. Here we identify a population of peripheral sensory neurons expressing TrkB that are both necessary and sufficient for producing pain from light touch after nerve injury in mice. Mice in which TrkB-Cre-expressing neurons are ablated are less sensitive to the lightest touch under basal conditions, and fail to develop mechanical allodynia in a model of neuropathic pain. Moreover, selective optogenetic activation of these neurons after nerve injury evokes marked nociceptive behavior. Using a phototherapeutic approach based upon BDNF, the ligand for TrkB, we perform molecule-guided laser ablation of these neurons and achieve long-term retraction of TrkB-positive neurons from the skin and pronounced reversal of mechanical allodynia across multiple types of neuropathic pain. Thus we identify the peripheral neurons which transmit pain from light touch and uncover a novel pharmacological strategy for its treatment.