The possibility of integrating motile sperm organelle morphology examination (MSOME) with intracytoplasmic morphologically-selected sperm injection (IMSI) when treating couples with unexplained infertility.
ABSTRACT: PURPOSE:To examine the efficacy of motile sperm organelle morphology examination (MSOME) and intracytoplasmic morphologically-selected sperm injection (IMSI) for unexplained infertility. METHODS:This historical study, included 271 couples with primary, unexplained infertility/male subfertility, treated at an outpatient, IVF clinic, 2015-2018. These couples underwent MSOME after ?3 failed intrauterine insemination (IUI) cycles and ?1 failed IVF-ICSI cycle. They proceeded to intracytoplasmic morphologically-selected sperm injection (IMSI) within 6 months of MSOME. IMSI is conducted on the day of oocyte pick-up with a fresh semen sample. Pregnancy and delivery rates were analyzed. RESULTS:The cohort was divided based on percentage of normal cells at MSOME: Group A included 55 with no normal cells, Group B, 184 with 0.5%? normal cells ?1.5% and Group C, 32 with ?2% normal cells. Normal spermatozoa were found in 49 (89%) of Group A after extensive search. Group A had higher pregnancy rate (62.7%) compared to B (47.2%, P = 0.05) and C (28.1%, P = 0.002). Group B had higher pregnancy rate than C (p = 0.045). Delivery rate was higher in Group A (52.1%) compared to B (34.1%, p = 0.023) and C (21.9%, p = 0.007). Pregnancy and delivery rates were higher in A compared to B+C (p = 0.018, p = 0.01, respectively). CONCLUSIONS:MSOME may be useful for evaluating unexplained infertility. IMSI can be recommended for men with <2% normal spermatozoa at MSOME.
Project description:Background:In the assisted reproduction, the infertile molecules of spermatozoa from normozoospermic men who underwent the unexplained failure of in vitro fertilization (IVF) due to the lack of sperm binding to the normal zona pellucida, and then achieved pregnancy with the rescue intracytoplasmic sperm injection (R-ICSI) remain unclear. More works are still necessary to explore this male infertile mechanism. Methods:Normozoospermicmen with the IVF pregnancy and normozoospermic men with the R-ICSI pregnancy after the conventional IVF failure were collected. iTRAQ-based proteomic approach were performed to reveal the new infertile causes between the IVF pregnancy men and the R-ICSI pregnancy men. To validate the confidence of proteome data, the individual samples were analyzed by western blot and immunofluorescence. Further, the spontaneous acrosome reactions were measured to evaluate the sperm quality. Results:Compared with IVF pregnancy group, 56 sperm proteins were differentially expressed in the R-ICSI pregnancy group. Bioinformatic analyses (PANTHER, DAVID, PubMed and STRING) indicated these altered sperm proteins were involved in various molecular functions: reproduction, chromosome organization, and sperm-oocyte interaction. Moreover, the confidence of proteome data was confirmed by western blot and immunofluorescence using the individual samples, which were consistent with our proteomic data. Additionally, an increased rate of the spontaneous acrosome reaction rate was found in the R-ICSI pregnancy group. Conclusions:The sealtered sperm proteins and the increased spontaneous acrosome reaction rate might account for this unexplained male infertility in the R-ICSI pregnancy patients. The present proteomic results will throw light on the better understanding of the unexplained infertile mechanisms underlying these normozoospermic man who achieved R-ICSI pregnancy after IVF failure.
Project description:Intracytoplasmic sperm injection (ICSI) is the recommended treatment in many cases of male-factor infertility. Several studies have demonstrated a positive correlation between optimal sperm morphology and positive ICSI outcomes. In fact, spermatozoa with severe abnormalities of the head are well documented to be associated with low fertilisation, implantation and pregnancy rates. However, a spermatozoon which is classified as 'normal' by microscopic observation at low magnification could contain ultrastructural defects that impair both the fertilisation process and embryonic development. The intracytoplasmic morphologically selected sperm injection (IMSI) procedure changed the perception of how a spermatozoon suitable for injection should appear. Sperm selection is carried out at ×6000 magnification, allowing improved assessment of the sperm nucleus. Currently, standardized clinical indications for IMSI are lacking and the candidates are selected on the grounds of their medical history or of a careful analysis of the sperm suspension. Further prospective randomized studies are needed to confirm the advantages of IMSI in specific groups of patients. In addition to providing a brief overview of the IMSI procedure, this study aims to review the literature, which explains the theoretical basis and the clinical outcomes of this technique. Several reports show that IMSI is associated with improved implantation and clinical pregnancy rates as well as lower abortion rates when compared to ICSI. Although a possible correlation between the sperm's abnormal nucleus shape, increased DNA fragmentation and negative laboratory and clinical outcomes has been long investigated, the results are conflicting.
Project description:Spermatid specific thioredoxin-3 (SPTRX3 or TXNDC8) is a testis/male germ line specific member of thioredoxin family that accumulates in the superfluous cytoplasm of defective human spermatozoa. We hypothesized that semen levels of SPTRX3 are reflective of treatment outcome in assisted reproductive therapy (ART) couples treated by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Relationship between SPTRX3 and treatment outcome was investigated in 239 couples undergoing ART at an infertility clinic. Sperm content of SPTRX3 was evaluated by flow cytometry and epifluorescence microscopy, and correlated with clinical semen analysis parameters, and data on embryo development and pregnancy establishment. High SPTRX3 levels (>15% SPTRX3-positive spermatozoa) were found in 51% of male infertility patients (n?=?72), in 20% of men from couples with unexplained, idiopathic infertility (n?=?61) and in 14% of men from couples previously diagnosed with female-only infertility (n?=?85). Couples with high SPTRX3 produced fewer two-pronuclear zygotes and had a reduced pregnancy rate (19.2% pregnant with >15% SPTRX3-positive spermatozoa vs. 41.2% pregnant with <5% SPTRX3-positive sperm; one-sided p<0.05). The average pregnancy rate of all 239 couples was 25.1%. Live birth rate was 19.2% and lowest average SPTRX3 levels were found in couples that delivered twins. Men with >15% of SPTRX3-positive spermatozoa, a cutoff value established by ROC analysis, had their chance of fathering children by IVF or ICSI reduced by nearly two-thirds. The percentage of SPTRX3-positive spermatozoa had predictive value for pregnancy after ART. Gradient purification and sperm swim-up failed to remove all SPTRX3-positive spermatozoa from semen prepared for ART. In summary, the elevated semen content of SPTRX3 in men from ART couples coincided with reduced incidence of pregnancy by IVF or ICSI, identifying SPTRX3 as a candidate biomarker reflective of ART outcome.
Project description:This study compared the cumulative live birth rates following Intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilization (cIVF) in women aged 40 years or more and unexplained infertility. A cohort of 685 women undergoing either autologous conventional IVF or ICSI was retrospectively analyzed. The effects of conventional IVF or ICSI procedure on cumulative pregnancy and live birth rates were evaluated in univariate and in multivariable analysis. In order to reduce potential differences between women undergoing either IVF or ICSI and to obtain unbiased estimation of the treatment effect, propensity score was estimated. ICSI was performed in 307 couples (ICSI group), whereas cIVF was performed in 297 couples (cIVF group), resulting in 45 and 43 live deliveries, respectively. No differences were observed in morphological embryo quality, in the number of cleavage stage embryos, in the number of transferred embryos, and in the number of vitrified embryos. As for the clinical outcome, no differences were observed in pregnancy rate, cumulative pregnancy rate, live birth rate, cumulative live birth rate, and abortion rate. The present results suggest that ICSI is not associated with increased likelihood of a live birth for unexplained, non-male factor infertility, in women aged 40 years or more.
Project description:We report a successful ongoing pregnancy obtained in a case of total globozoospermia after intracytoplasmic morphologically selected sperm injection (IMSI) with oocyte activation. The first semen analysis on investigation showed partial globozoospermia. However, under high magnification assessment at oocyte retrieval only round headed sperm were observed. Considering the high risk of a complete failure to fertilize from IMSI the couple gave written informed consent to the use of oocyte activation media post IMSI. One embryo fertilized, developed to a hatching blastocyst and was transferred resulting in an ongoing pregnancy. This successful outcome shows the use of IMSI is useful in the evaluation of total globozooozpermia and therefore aids in the justification of the use of oocyte activation media.
Project description:INTRODUCTION:Intracytoplasmic sperm injection (ICSI), originally introduced as add-on to in vitro fertilisation (IVF) for couples with severe male infertility, is in current clinical practice also used in couples with mild male or even unexplained infertility. However, ICSI has involved unresolved concerns regarding the selection and damage to gametes and the health conditions of the offspring, and it is also labour intensive and therefore more expensive than conventional IVF. High-quality well-powered randomised clinical trials (RCTs) comparing ICSI and IVF are lacking. METHODS AND ANALYSIS:We propose a multicentre, open-label RCT in 10 reproductive medical centres across China. We will study couples with non-severe male infertility (defined as a semen concentrate 5-15×106/mL or sperm with a progressive motility 10%-32%) scheduled for their first or second ICSI or IVF cycle, as low fertility rate after fertilisation are more frequent in this population, which could lead to controversy about ICSI or conventional IVF for fertilisation. On the day of oocyte retrieval, eligible participants are after informed consent be randomised to undergo either ICSI or conventional IVF in a 1:1 treatment ratio. Other standard assisted reproductive treatments are similar and parallel between two groups. Our primary outcome is ongoing pregnancy leading to live birth after the first cycle with embryo transfer. To demonstrate or refute a difference of 7% between ICSI and conventional IVF, we need to include 2346 women (1173 in each intervention arm). In addition, we will follow-up neonatal outcomes after delivery to identify the influence of ICSI on offspring. ETHICS AND DISSEMINATION:Ethical approval was obtained from Peking University Third Hospital medical science research ethics committee. The findings will be disseminated to the public through conference presentations and peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov registry (NCT03298633).
Project description:To determine the cost-effectiveness of split IVF-intracytoplasmic sperm injection (ICSI) for the treatment of couples with unexplained infertility.Adaptive decision model.Academic infertility clinic.A total of 154 couples undergoing a split IVF-ICSI cycle and a computer-simulated cohort of women <35 years old with unexplained infertility undergoing IVF.Modeling insemination method in the first IVF cycle as all IVF, split IVF-ICSI, or all ICSI, and adapting treatment based on fertilization outcomes.Live birth rate, incremental cost-effectiveness ratio (ICER).In a single cycle, all IVF is preferred as the ICER of split IVF-ICSI or all ICSI ($58,766) does not justify the increased live birth rate (3%). If two cycles are needed, split IVF/ICSI is preferred as the increased cumulative live birth rate (3.3%) is gained at an ICER of $29,666.In a single cycle, all IVF was preferred as the increased live birth rate with split IVF-ICSI and all ICSI was not justified by the increased cost per live birth. If two IVF cycles are needed, however, split IVF/ICSI becomes the preferred approach, as a result of the higher cumulative live birth rate compared with all IVF and the lesser cost per live birth compared with all ICSI.
Project description:The acrosome of the spermatozoa is required for fertilization and in the raw ejaculate the percentage of viable acrosome-intact spermatozoa, the acrosomal status, is higher among men with good semen quality. Here we investigated if the acrosomal status of the processed semen preparations used at a fertility clinic can also be informative and whether it is associated with fecundity. The acrosomal status was measured by image cytometry on purified semen samples from couples during in vitro fertilization (IVF) (n = 99) and intracytoplasmic sperm injection (ICSI) (n = 107) treatment. Purified frozen-thawed donor samples were also analyzed (n = 199). In purified semen preparations the acrosomal status was significantly higher among sperm donors (p = 5.3 × 10-8) and men from IVF couples (p = 2.2 × 10-5) when compared to men from ICSI couples. A significant difference was also found between female, male and mixed factor infertility (p = 0.003). No association with lifestyle factors was found. In frozen-thawed donor samples, a significant positive (r = 0.16, p = 0.025) association with the number of pregnancies per sold straw was observed together with an area under the curve of 75.3%, when comparing the top and bottom deciles. Our results indicate that the acrosomal status may be a valuable parameter for personalizing fertility treatments and might be a good predictor of pregnancy success among normozoospermic men.
Project description:Intracytoplasmic morphologically selected sperm injection (IMSI) is still proposed and employed in the clinical practice to improve the reproductive outcome in infertile couples scheduled for conventional intracytoplasmic sperm injection (cICSI). The aim of the current randomized controlled trial (RCT) was to test the hypothesis that IMSI gives a better live birth delivery rate than cICSI.Infertile couples scheduled for their first cICSI cycle for male factor were allocated using a simple randomization procedure. All available biological and clinical data were recorded and analyzed in a triple-blind fashion.Our final analysis involved the first 121 patients (48 and 73 subjects for IMSI and cICSI arm, respectively) because the trial was stopped prematurely on the advice of the data safety and monitoring Committee because of concerns about IMSI efficacy at the first interim analysis. No significant difference between arms was detected in rates of clinical pregnancy per embryo transferred [11/34 (32.3%) vs. 15/64 (23.4%); odds ratio (OR) 1.56, 95% (confidence interval) CI 0.62-3.93, P = 0.343] and of live birth delivery [9/48 (18.8%) vs. 11/73 (15.1%); OR 1.30, 95%CI 0.49-3.42, P = 0.594).Current data did not support the routine use of IMSI in the clinical practice for improving cICSI results in unselected infertile couples with male factor.
Project description:Infertility affects 10 to 15% of couples worldwide, with a male factor contributing up to 50% of these cases. The primary tool for diagnosing male infertility is traditional semen analysis, which reveals sperm concentration, morphology, and motility. However, 25% of infertile men are diagnosed as normozoospermic, meaning that, in many cases, normal-appearing sperm fail to fertilize an egg. Thus, new information regarding the mechanisms by which sperm acquire fertilizing ability is needed to develop a clinically feasible test that can predict sperm function failure. An important feature of sperm fertilization capability in many species is plasma membrane hyperpolarization (membrane potential becoming more negative inside) in response to signals from the egg or female genital tract. In mice, this hyperpolarization is necessary for sperm to undergo the changes in motility (hyperactivation) and acrosomal exocytosis required to fertilize an egg. Human sperm also hyperpolarize during capacitation, but the physiological relevance of this event has not been determined. Here, we used flow cytometry combined with a voltage-sensitive fluorescent probe to measure absolute values of human sperm membrane potential. We found that hyperpolarization of human sperm plasma membrane correlated positively with fertilizing ability. Hyperpolarized human sperm had higher in vitro fertilization (IVF) ratios and higher percentages of acrosomal exocytosis and hyperactivated motility than depolarized sperm. We propose that measurements of human sperm membrane potential could be used to diagnose men with idiopathic infertility and predict IVF success in normozoospermic infertile patients. Patients with depolarized values could be guided toward intracytoplasmic sperm injection, preventing unnecessary cycles of intrauterine insemination or IVF. Conversely, patients with hyperpolarized values of sperm membrane potential could undergo only conventional IVF, avoiding the risks and costs associated with intracytoplasmic sperm injection.