Semen cryopreservation in men undergoing cancer treatment: a ten-year study.

BACKGROUND: The advancement of Assisted Reproductive Technologies and the improvement in sperm freezing made male fertility preservation widely available. This study aims to evaluate the impact of cancer diseases on semen parameters before cryopreservation and the reproductive outcomes of patients who have thawed their semen samples. METHODS: An observational, cohort study was conducted on cancer patients submitted to fertility preservation in AUSL-IRCCS of Reggio Emilia between 2007 and 2018. Semen samples were collected before cancer treatments, analyzed and frozen by rapid freezing. On request, these samples were thawed for Assisted Reproductive Technologies procedures. Semen parameters were compared between testicular versus other cancers. RESULTS: We included 329 patients with a successful cryopreservation in 94.5% of cases. Testicular cancer was associated with lower sperm volumes (P=0.041) and lower total sperm concentration (P=0.009) compared to other cancers. No difference was observed about sperm motility and morphology, while oligozoospermia was significantly more frequent in men with testicular cancer (P<0.001). In our cohort, the 8.4% of patients thawed their samples; the usage rate and the embryo transfer rate were significantly higher (P<0.05) among those with a testicular cancer, while pregnancy and livebirth rates did not differ. CONCLUSIONS: Male fertility preservation is feasible, easy to be performed, non-invasive and does not delay cancer treatments. Men affected by testicular cancer had worse semen parameters at cryopreservation but pregnancy and livebirth rates were similar to those achieved by men with other cancers and similar to those achieved with fresh sperm.

A Customized Tool of Incident Reporting for the Detection of Nonconformances at a Single IVF Center: Development, Application, and Efficacy.

In IVF centers, risk assessment applies to complex processes potentially accounting for adverse events and reactions that undergo well-established legislative oversight, and nonconformances (NCs), that lack of established tracking systems. NCs account for an integral part of the quality management system, so that their documentation is important. The study evaluated the performance of a customized tool for incident reporting (IR) to track and characterize NCs in a public IVF center. IVF operators used the IVF-customized IR tool to record NCs at the moment of detection or subsequently, and in a time-saving manner during daily practice. From February 2015 to February 2020, 635 NCs were reported leading to the implementation of 10 operative instructions and 3 procedures with corrective strategies. NCs referred to the IVF laboratory were the most numerically meaningful (454/635, 71.5%). The majority (352/454, 77.5%) accounted for NCs related to procedures of sample management; considering the analytical phase as all the procedures involving sample treatment, the intra-analytical phase (176/352, 50%) has always been more subject to NCs compared to pre- (102/352, 29%) and postanalytical (74/352, 21%) phases. Our experience showed that the IVF-customized IR tool is suitable for application in IVF with regard to NC reports and documentation, as it identifies the most vulnerable steps of treatments. It manages NCs over the time, but it requires a contextual understanding of its application in order to avoid NC underestimates that could negatively influence the safety and quality aspects of IVF treatments.

Improvement of sperm morphology after surgical varicocele repair.

BACKGROUND: A causative relationship between varicocele and impairment of semen quality has been largely investigated in the context of male infertility, although its clinical benefit remains controversial. OBJECTIVE: To investigate the effect of varicocele correction on detailed morphologic microscopic semen parameters in a large homogeneous cohort of patients and to evaluate which factors could predict semen improvement after the surgical treatment. MATERIALS AND METHODS: An observational, retrospective cohort study was carried out including all patients undergoing surgical treatment for varicocele from September 2011 to March 2020 in the same clinical centre. Enrolled males performed at least one semen analysis before and one after surgical varicocele correction. Primary outcome was the detailed morphologic microscopic sperm evaluation. Secondary outcomes were conventional semen analyses. RESULTS: A total of 121 males (mean age 24.6 ± 6.1 years) were enrolled. Using detailed morphologic microscopic sperm evaluation, a significant morphological improvement was recorded, with a reduction in head and tail abnormalities. Moreover, a significant increase in sperm concentration (p = 0.015) and percentage of progressive and total motility (p = 0.022 and p = 0.039) were observed after surgery. The multivariate logistic analysis identified the ultrasonography varicocele degree before surgery as a main predictor of the sperm concentration improvement (p = 0.016), with the highest improvement for varicocele of I and II degree. DISCUSSION: For the first time, the detailed morphologic microscopic sperm evaluation highlights a relevant reduction in sperm abnormalities after varicocele surgery, showing its potential application in clinical practice.

Intracytoplasmic morphologically selected sperm injection versus conventional intracytoplasmic sperm injection: a randomized controlled trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Physical activity before IVF and ICSI cycles in infertile obese women: an observational cohort study.

This study assessed the relationship between regular physical activity and reproductive performance in obese infertile patients who receive assisted reproduction cycles with stable bodyweight. A total of 216 obese infertile women at their first fresh assisted reproduction attempt with stable body mass index (BMI) and available data on their physical activity carried out up to the beginning of the treatment cycle were enrolled in this observational cohort study. Clinical and biological data were recorded and analysed. There were 41 obese patients who did regular physical activity and 175 obese controls who did not. Total pregnancies (16/41, 39.0% versus 28/175, 16.0%, respectively; P = 0.002) and live births (10/41, 24.4% versus 13/175, 7.4%, respectively; P = 0.004) were significantly higher in patients who did physical activity regularly compared with those who did not. After adjusting for confounders, in obese infertile patients who did physical activity regularly, the relative risks for a clinical pregnancy and live birth were 3.22 (95% CI 1.53-6.78; P = 0.002) and 3.71 (95% CI 1.51-9.11; P = 0.004), respectively. In conclusion, regular physical activity carried out before a assisted reproduction cycle is significantly related with improved reproductive performance in obese infertile patients, irrespective of bodyweight loss. Body weight loss improves not only spontaneous pregnancy rates but also those of assisted reproductive techniques (ARTs). Moreover, almost all studies refer to body weight loss due to lifestyle intervention programs consisting in hypocaloric diet and increased physical activity. Instead, very little is known about the specific effects of physical activity alone on human reproduction. Based on these considerations, we designed the present study to assess the relationship between regular physical activity and reproductive outcome in infertile obese patients who receive ARTs. Two-hundred-sixteen obese infertile women with stable body mass index (BMI) and at their first fresh ART attempt were enrolled, and clinical and biological data were recorded and analyzed. Our results demonstrate that the chances to obtain a pregnancy and a baby are 3-fold higher in obese infertile patients who does physical activity regularly in comparison with those who does not, suggesting that regular physical activity before ART cycles improves the reproductive performance in obese women irrespective to body weight loss.

Pronuclear morphology evaluation in in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) cycles: a retrospective clinical review.

BACKGROUND: The assessment of the embryo quality is crucial to maintain an high pregnancy rate and to reduce the risk of multiple pregnancy. The evaluation of the pronuclear and nucleolar characteristics of human zygote have been proposed as an indicator of embryo development and chromosomal complement. The aim of the current study was to assess the role of pronuclear morphology evaluation in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) cycles. METHODS: Retrospective clinical analysis on 755 non-elective transfers of only one embryo (ET). Embryo assessment was performed in days 1 and 2. Clinical and biological data were recorded and analyzed according to embryo and/or pronuclear morphology. RESULTS: Both pronuclear and embryo morphology were significantly related to clinical pregnancy and live-birth rates. No significant difference in clinical pregnancy and live-birth rates was detected when the pronuclear and embryo morphology assessments were combined. Embryo morphology and maternal age were the only independent predictors of favorable outcome by logistic regression analysis. CONCLUSIONS: Pronuclear evaluation is effective to select the best zygotes if ET is performed at day 1, whereas it did not improve the clinical outcomes when combined with embryo morphology evaluation in day 2.

Impact of insemination technique, semen quality and oocyte cryopreservation on pronuclear morphology of zygotes derived from sibling oocytes.

Pronuclear morphology seems to be an important predictive value of zygote development and integrity. In this study we want to evaluate the effect of insemination technique, male factor and oocyte cryopreservation on pronuclear morphology of zygotes derived from sibling oocytes in our Centre of Reproductive Medicine, Department of Obstetrics and Gynecology, Arcispedale S. Maria Nuova, Reggio Emilia, Italy. Subjects (n = 190) were submitted to IVF cycles with non-frozen and frozen sibling oocytes. Morphological evaluations were assessed using zygote pronuclear morphology (pronuclei, nucleoli and axis) in four groups: Group 1: 144 zygotes from 85 conventional IVF cycles with non-frozen oocytes; Group 2: 164 zygotes from 85 intracytoplasmic sperm injection (ICSI) cycles with Group 1 patients' sibling frozen oocytes; Group 3: 221 zygotes from 123 ICSI cycles with non-frozen oocytes; Group 4: 197 zygotes from 123 ICSI cycles with Group 3 patients' sibling frozen oocytes. No differences between Group 1 and Group 2 were seen. Group 3 was statistically different from Group 4 in relation to the nucleolar morphology. Oocyte cryopreservation procedure modified the nucleolar morphology of zygotes only in the presence of poor semen quality.

Nitric oxide as an early marker of human embryo metabolic cleavage in ART using fresh or thawed oocytes.

OBJECTIVE: To study a possible role of nitric oxide (NO) as a marker of development in the early phases of human embryo cleavage during assisted reproduction. STUDY DESIGN: 179 women having ART were included. 123 women used fresh oocytes and 56 oocyte thawing cycles in the Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Arcispedale S. Maria Nuova, between July 2005 and June 2006; 57 patients had IVF and 122 patients had ICSI. NO concentrations in IVF or ICSI embryo culture media were assessed by monitoring levels of NO stable oxidation products (nitrites/nitrates). Analysis of embryo quality was performed. Student's t-test or Mann-Whitney and logistic regression model tests were applied to the data. RESULTS: In patients using fresh oocytes, there were greater NO production in embryos derived from ICSI than from IVF after 52 h of culture (38.64 micromol/L vs 11.2 micromol/L, p<0.05). No correlation with embryo quality was observed. Embryos derived from fresh oocytes produce more NO than embryos from thawed oocytes both after 48 and 52 h of culture (16.12 micromol/L vs 6.83 micromol/L and 25.93 micromol/L vs 2.98 micromol/L respectively, p<0.05). CONCLUSION(S): NO in embryo culture media is not a metabolic cleavage marker or a marker of embryo quality in ART. However, it could be an important parameter in the investigation of metabolism in frozen/thawed oocytes.

The effect of legislation on outcomes of assisted reproduction technology: lessons from the 2004 Italian law.

OBJECTIVE: To evaluate the effect of the 2004 Italian regulations (insemination of

Limited importance of pre-embryo pronuclear morphology (zygote score) in assisted reproduction outcome in the absence of embryo cryopreservation.

OBJECTIVE: To investigate the hypothesis that Z-score criteria represent a reliable predictor of implantation rate and pregnancy outcome in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles, excluding the possibility of embryo selection before the embryo transfer. DESIGN: Retrospective clinical study. SETTING: Centre of Reproductive Medicine, Department of Obstetrics and Gynecology, Arcispedale S. Maria Nuova (ASMN), Reggio Emilia, Italy. PATIENT(S): We analyzed 393 pregnancies obtained by IVF or ICSI cycles. INTERVENTION(S): Morphologic evaluations of Z-score in pre-embryos obtained from IVF or ICSI cycles. MAIN OUTCOME MEASURE(S): Evaluations of Z-scores, implantation rate, and clinical pregnancy outcome. RESULT(S): We did not find any statistically significant correlation between the Z-score of 1032 embryos transferred in 393 embryo transfers and the implantation rate or the pregnancy outcome. In particular, the best Z-score identified (Z1, 7.2%) did not seem to correlate with embryo implantation rate or pregnancy outcomes any better than those with worse scores (Z2, 6.9% and Z3, 85.9%). CONCLUSION(S): Our results seem to confirm that Z-score alone cannot be considered a better tool than standard morphologic criteria for identifying, controlling, or selecting embryos with a better chance of successful ongoing pregnancy.

Testicular sperm aspiration (TESA) in 327 ICSI cycles.

OBJECTIVE: To evaluate the efficiency of testicular sperm recovery by testicular sperm aspiration (TESA) in an IVF program. DESIGN: Retrospective Data Analysis. SETTING: The Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Arcispedale S. Maria Nuova, Reggio Emilia, Italy. PATIENT(S): Couples undergoing TESA/ICSI for obstructive or nonobstructive azoospermia. INTERVENTION(S): ESA/ICSI. MAIN OUTCOME MEASURE(S): Efficiency of testicular sperm recovery, fertilization rate, implantation rate and clinical pregnancy rate. RESULT(S): Between March 1, 1997 and March 31, 2005, 327 cycles of TESA/ICSI were performed in couples in which the male had obstructive or nonobstructive azoospermia. The efficiency of testicular sperm recovery was 99.4% and 99.3%, fertilization rate 57.1% and 49.1%, implantation rate 5.7% and 6.2%, and the clinical pregnancy rate 12.9% and 15.4% in men with obstructive and nonobstructive infertility, respectively. CONCLUSION(S): The efficiency of TESA is very high in both obstructive and nonobstructive azoospermia. Because TESA is less invasive than TESE, it should be considered a valuable alternative to TESE in IVF programs, especially in setting where resources are limited.