Intracytoplasmic sperm injection versus conventional in vitro fertilisation in couples with males presenting with normal total sperm count and motility.

BACKGROUND: Starting over 40 years ago, in vitro fertilisation (IVF) has become the cornerstone for fertility treatment. Since then, in 1992, Palermo and colleagues successfully applied the technique intracytoplasmic sperm injection (ICSI) to benefit couples where conventional in vitro fertilisation (c-IVF) and sub-zonal insemination (SUZI) proved unsuccessful. After this case report, ICSI has become the treatment of choice for couples with severe male factor subfertility. Over time, ICSI has been used in the treatment of couples with mild male and even unexplained infertility. This review is an update of the review, first published in 1999, comparing ICSI with c-IVF for couples with males presenting with normal total sperm count and motility. OBJECTIVES: To evaluate the effectiveness and safety of ICSI relative to c-IVF in couples with males presenting with normal total sperm count and motility. SEARCH METHODS: We searched the following databases and trial registers: Cochrane Central Register of Controlled Trials (CENTRAL), Embase (excerpta Medica Database), MEDLINE (Medical Literature Analysis and Retrieval System Online) and PsycINFO (Psychological literature database) for articles between January 2010 and 22 February 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared ICSI with c-IVF in couples with males presenting with normal total sperm count and motility. DATA COLLECTION AND ANALYSIS: We used standard methodical procedures recommended by Cochrane. The primary review outcomes were live birth and adverse events. Secondary outcomes included clinical pregnancy, viable intrauterine pregnancy and miscarriage. MAIN RESULTS: The original review published in 2003 included one RCT. In this 2023 update, we identified an additional two RCTs totalling a cohort of 1539 couples, comparing ICSI with c-IVF techniques. Two studies reported on live birth. Using the GRADE method, we assessed the certainty of evidence and reported evidence as low-certainty for live birth. We are uncertain of the effect of ICSI versus c-IVF for live birth rates (risk ratio (RR) 1.11, 95% confidence interval (CI 0.94 to 1.30, I2 = 0%, 2 studies, n = 1124, low-certainty evidence). The evidence suggests that if the chance of live birth following c-IVF is assumed to be 32%, the chance of live birth with ICSI would be between 30% and 41%. For adverse events; multiple pregnancy, ectopic pregnancy, pre-eclampsia and prematurity, there was probably little or no difference between the two techniques. No study reported the primary outcome stillbirth. For secondary outcomes, we are uncertain of the effect of ICSI versus c-IVF for clinical pregnancy rates (RR 1.00, 95% CI 0.88 to 1.13, I2 = 45%, 3 studies, n = 1539, low-certainty evidence). Comparison of viable intrauterine pregnancy rates showed probably little or no difference between ICSI and c-IVF (RR 1.00, 95% CI 0.86 to 1.16, I2=75%, 2 studies, n = 1479 couples, moderate-certainty evidence). The high heterogeneity may have been caused by one older study conducted when protocols were less rigorous. The evidence suggests that if the chance of viable intrauterine pregnancy following c-IVF is assumed to be 33%, the chance of viable intrauterine pregnancy with ICSI would be between 28% and 38%. Miscarriage rates also showed probably little or no difference between the two techniques. AUTHORS' CONCLUSIONS: The current available studies that compare ICSI and c-IVF in couples with males presenting with normal total sperm count and motility, show neither method was superior to the other, in achieving live birth, adverse events (multiple pregnancy, ectopic pregnancy, pre-eclampsia and prematurity), also alongside secondary outcomes, clinical pregnancy, viable intrauterine pregnancy or miscarriage.

The Effect of Dietary Patterns on Clinical Pregnancy and Live Birth Outcomes in Men and Women Receiving Assisted Reproductive Technologies: A Systematic Review and Meta-Analysis.

The nutritional status of reproductive-aged couples can have a significant impact on fertility status, but the effect of dietary patterns on pregnancy outcomes in people using assisted reproductive technologies (ARTs) is currently unknown. This review aimed to synthesize the published research investigating the relation between preconception dietary patterns and clinical pregnancy or live birth in men and women of reproductive age undergoing ART. Six electronic databases were systematically searched for original research published between January 1978 and June 2021. Original research reporting on the effect of predefined dietary patterns on either clinical pregnancy and/or live birth rates following in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in men and women aged 18-49 y was eligible for inclusion. Studies were assessed for risk of bias according to the Cochrane guidelines. Included studies underwent qualitative and quantitative synthesis using random-effects model meta-analyses. Thirteen studies (12 cohort studies, 1 randomized controlled trial) reporting on 3638 participants (93% female) were included in the review. All studies had a moderate-high risk of bias. In individual studies, maternal adherence to 4 dietary patterns [Mediterranean diet (RR: 1.22; 95% CI: 1.05, 1.43), novel profertility diet (OR: 1.43; 95% CI: 1.19, 1.72), Iranian traditional medicine diet (OR: 3.9; 95% CI: 1.2, 12.8), Dutch national dietary recommendations diet (OR: 1.65; 95% CI: 1.08, 2.52)] was associated with increased likelihood of achieving a clinical pregnancy, while 2 dietary patterns [novel profertility diet (OR: 1.53; 95% CI: 1.26, 1.85), Mediterranean diet (RR: 1.25; 95% CI: 1.07, 1.45)] were associated with increased probability of live birth. Meta-analyses showed an association between adherence to the Mediterranean dietary pattern and live birth across 2 studies (OR: 1.98; 95% CI: 1.17, 3.35; I2 = 29%, n = 355), but no association with clinical pregnancy. As the relation between dietary patterns and ART outcomes is currently inconsistent, higher-quality nutrition research is required to further explore this emerging field of interest (PROSPERO registration: CRD42020188194).

Calcium chloride dihydrate supplementation at ICSI improves fertilization and pregnancy rates in patients with previous low fertilization: a retrospective paired treatment cycle study.

PURPOSE: To determine if 5mM calcium chloride dihydrate supplementation of the Polyvinylpyrrolidone (PVP) media at the time of ICSI (ICSI-Ca) improves fertilization, utilization, and clinical pregnancy rates compared to ICSI alone, particularly in patients with a history of low fertilization (< 50%). METHODS: Retrospective study between 2016 and 2021 at Monash IVF Victoria on a paired cohort of patients (n = 178 patients) where an ICSI cycle was analyzed coupled with the subsequent ICSI-Ca cycle. The paired cohort was further subdivided into a low-fertilization cohort (< 50% fertilization on previous cycles: n = 66 patients) compared to the remaining patients with fertilization ≥ 50% (n = 122). Exclusion criteria included donor cycles, PGT patients, surgical sperm retrieval, women ≥ 45 years old, patients with > 6 cycles, and patients with ≤ 5 inseminated oocytes. RESULTS: Calcium supplementation significantly increased both fertilization (28.8% ICSI vs 49.7% ICSI-Ca, P < 0.0001) and clinical pregnancy rate (4.9% ICSI vs 25.0% ICSI-Ca: P < 0.05) in the low-fertilization cohort but not in the normal-fertilization cohort. Interestingly, utilization rate significantly increased in the normal-fertilization cohort (32.6% ICSI vs ICSI-Ca: 44.9%, P < 0.01) but not in the low-fertilization cohort, although the number of embryos utilized per patient after ICSI-Ca increased in both groups. CONCLUSION: Calcium supplementation does not appear to be a detrimental addition to ICSI and may improve IVF outcomes, particularly for patients with a history of low fertilization. Further investigations including prospective case-matched studies or a RCT are required to confirm these findings.

The impact of COVID-19 mitigation measures on fertility patients and clinics around the world.

RESEARCH QUESTION: What is the impact of the response to COVID-19 on the management of fertility treatments and clinical practice around the world? DESIGN: Fertility clinic associates around the world were approached. They completed an online survey containing 33 questions focused on the country's response to the COVID-19 pandemic. Known fertility clinic associates that were contacted comprised scientific directors, medical directors and laboratory managers. RESULTS: There were 43 individual country responses from Asia (13), Africa (3), Europe (17), North America (3), Oceania (2) and South America (5). In nine countries, clinics followed their government body recommendations, in 22 countries there was a combination of recommendations, in 3 countries changes were made by clinic initiative, and 9 countries did not specify. In 34 countries IVF/intracytoplasmic sperm injection (ICSI) and frozen embryo transfer (FET) treatments had an average delay of 56 days (IVF/ICSI) (minimum 0, maximum 160) and 57 days (FET) (minimum 0, maximum 166 days). During the shutdown, the number of freeze-all cycles increased in 22 countries. Only 23 countries reported patients having to undergo a SARS-CoV-2 test, and 20 countries did not report any COVID-19 testing in their clinic. Additional support counselling was offered in 28 countries, partner restrictions at clinics were reported in 41 countries and time between patients' appointments was increased in 39 countries. CONCLUSIONS: The implications of COVID-19 mitigation measures proved the need for government societies to introduce a set protocol that includes requirements such as increased patient counselling and additional guidelines for prioritizing couples who need care most urgently.

Ageing and ovarian stimulation modulate the relative levels of transcript abundance of oocyte DNA repair genes during the germinal vesicle-metaphase II transition in mice.

PURPOSE: Oocyte quality and reproductive outcome are negatively affected by advanced maternal age, ovarian stimulation and method of oocyte maturation during assisted reproduction; however, the mechanisms responsible for these associations are not fully understood. The aim of this study was to compare the effects of ageing, ovarian stimulation and in-vitro maturation on the relative levels of transcript abundance of genes associated with DNA repair during the transition of germinal vesicle (GV) to metaphase II (MII) stages of oocyte development. METHODS: The relative levels of transcript abundance of 90 DNA repair-associated genes was compared in GV-stage and MII-stage oocytes from unstimulated and hormone-stimulated ovaries from young (5-8-week-old) and old (42-45-week-old) C57BL6 mice. Ovarian stimulation was conducted using pregnant mare serum gonadotropin (PMSG) or anti-inhibin serum (AIS). DNA damage response was quantified by immunolabeling of the phosphorylated histone variant H2AX (γH2AX). RESULTS: The relative transcript abundance in DNA repair genes was significantly lower in MII oocytes compared to GV oocytes in young unstimulated and PMSG stimulated but was higher in AIS-stimulated mice. Interestingly, an increase in the relative level of transcript abundance of DNA repair genes was observed in MII oocytes from older mice in unstimulated, PMSG-stimulated and AIS-stimulated mice. Decreased γH2AX levels were found in both GV oocytes (82.9%) and MII oocytes (37.5%) during ageing in both ovarian stimulation types used (PMSG/AIS; p < 0.05). CONCLUSIONS: In conclusion, DNA repair relative levels of transcript abundance are altered by maternal age and the method of ovarian stimulation during the GV-MII transition in oocytes.

Macrozoospermia associated with mutations of AURKC gene: first case report in Latin America and literature review / Macrozoospermia asociada con mutaciones del gen AURKC: primer caso clínico en Latinoamérica y revisión de la bibliografía

A Chilean 35-year-old male patient with a history of primary infertility made an appointment at the Unit of Reproductive Medicine at Clínica Las Condes, Santiago, Chile. Multiple semen analyses revealed abnormal sperm morphology as the most prevalent finding. Multiflagellated and macrocephalic spermatozoa were observed and indicated a possible macrozoospermic phenotype. The constant presence of abnormal sperm morphology led the scope of the study to include Aurora Kinase C (AURKC) gene sequencing. The patient was diagnosed with a homozygous mutation of this gene. The mutation was detected in exon 6, type c.744C>G+/+ (P.Y248*) variant. As previously described in the Human Gene Mutation Database (HGMD), this pathogenic variant is associated with macrozoospermia. Although this mutation is not the most frequently observed, it is the first of its kind reported in Latin America

Un chileno de 35 años con antecedentes de infertilidad primaria consultó en la Unidad de Medicina Reproductiva de la Clínica Las Condes, Santiago, Chile. Múltiples espermiogramas revelaron una morfología anormal de los espermatozoides como la anomalía más relevante. Se observaban espermatozoides multiflagelados y macrocefálicos, lo que indicaba un fenotipo de macrozoospermia. La uniformidad del patrón observado condujo a ampliar el enfoque del estudio hacia la secuenciación del gen cinasa Aurora C (AURKC). Al paciente se le diagnosticó una mutación homocigota de este gen. La mutación fue detectada en el exón 6, con la variante c.744C>G+/+ (P.Y248*). Como se ha descrito anteriormente en la Base de Datos de Mutaciones de Genes Humanos (HGMD), esta variante patogénica se asocia a macrozoospermia. Aunque esta mutación no es la que se observa con más frecuencia, es la primera de su tipo notificada en Latinoamérica

Macrozoospermia associated with mutations of AURKC gene: First case report in Latin America and literature review.

A Chilean 35-year-old male patient with a history of primary infertility made an appointment at the Unit of Reproductive Medicine at Clínica Las Condes, Santiago, Chile. Multiple semen analyses revealed abnormal sperm morphology as the most prevalent finding. Multiflagellated and macrocephalic spermatozoa were observed and indicated a possible macrozoospermic phenotype. The constant presence of abnormal sperm morphology led the scope of the study to include Aurora Kinase C (AURKC) gene sequencing. The patient was diagnosed with a homozygous mutation of this gene. The mutation was detected in exon 6, type c.744C>G+/+ (P.Y248*) variant. As previously described in the Human Gene Mutation Database (HGMD), this pathogenic variant is associated with macrozoospermia. Although this mutation is not the most frequently observed, it is the first of its kind reported in Latin America.

Minimal volume vitrification of epididymal spermatozoa results in successful in vitro fertilization and embryo development in mice.

This study compared three cryopreservation protocols on sperm functions, IVF outcomes, and embryo development. Epididymal spermatozoa cryopreserved using slow-cooling (18% w/v raffinose, RS-C) were compared with spermatozoa vitrified using 0.25 M sucrose (SV) or 18% w/v raffinose (RV). The motility, vitality, and DNA damage (TUNEL assay) of fresh control (FC) spermatozoa were compared with post-thawed or warmed RS-C, RV, and SV samples. Mouse oocytes (n = 267) were randomly assigned into three groups for insemination: RV (n = 102), RS-C (n = 86), and FC (n = 79). The number and the proportion of two-cell embryos and blastocysts from each treatment were assessed. Sperm motility (P < 0.01) and vitality (P < 0.05) were significantly reduced after vitrification compared with slow-cooled spermatozoa. However, DNA fragmentation was significantly reduced in spermatozoa vitrified using sucrose (15 ± 1.8% [SV] vs 26 ± 2.8% [RV] and 27 ± 1.2% [RS-C]; P < 0.01). Although the number of two-cell embryos produced by RS-C, RV, and FC spermatozoa was not significantly different, the number of blastocysts produced from two-cell embryos using RV spermatozoa was significantly higher than FC spermatozoa (P = 0.0053). This simple, small volume vitrification protocol and standard insemination method allows successful embryo production from small numbers of epididymal spermatozoa and may be applied clinically to circumvent the need for ICSI, which has the disadvantage of bypassing sperm selection.

[Association of age with sperm DNA fragmentation]. / Aumento del daño en el ADN espermático en varones mayores de 40 años.

BACKGROUND: There is an association between aging ana an increased number of sperms with alterations in nuclear DNA. AIM: To study the association between age and fragmentation of sperm DNA. MATERIAL AND METHODS: Sixty two volunteers provided semen for analysis. These were separated in a group aged less than forty years and a second group aged more than forty years. Sperm DNA fragmentation was studied by TUNEL (terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end-labeling) and SCD (sperm chromatin dispersion test) assays. RESULTS: Compared with their younger counterparts, patients aged more than 40 years had a higher proportion of sperms with DNA fragmentation by TUNEL (20 ± 1.3 and 24 ± 1.9% respectively, p < 0.05) and SCD (22 ± 1.4 and 26 ± 1.6% respectively, p < 0.05). The results of both assays had a correlation coefficient of O.8. No differences between groups were observed for other seminal parameters. CONCLUSIONS: Sperm DNA fragmentation increases with age in males.

Aumento del daño en el ADN espermático en varones mayores de 40 años / Association of age with sperm DNA fragmentation

Background: There is an association between aging ana an increased number ofsperms with alterations in nuclear DNA. Aim: To study the association between age and fragmentation of sperm DNA. Material andMethods: Sixty two volunteers provided semen for analysis. These were separated in a group aged less than forty years and a second group aged more than forty years. Sperm DNA fragmentation was studied by TÚNEL (terminal deoxynucleotidyl transferase-mediated2'-deoxyuridine 5'-triphosphate nick end-labeling) and SCD (sperm chromatin dispersión test) assays. Results: Compared with theiryounger counterparts, patients aged more than 40years had a higher proportion ofsperms with DNA fragmentation by TÚNEL (20 ±1.3 and24 ± 1.9 percent respectively, p < 0.05) and SCD (22 ± 1.4 and26 ± 1.6 percent respectively, p < 0.05). The results ofboth assays had a correlation coefficientofO.8. No differences between groups were observed for other seminal parameters. Conclusions: Sperm DNA fragmentation increases with age in males.