Effect of time since vasectomy on live birth rate of TESE‒ICSI egg donation cycles and male-related prognostic factors.

BACKGROUND: Vasectomy is a widely used method of contraception. However, some men may have the desire to become biological fathers again after a period. OBJECTIVE: To explore the effect of time since vasectomy and different male comorbidities on live birth rates from intracytoplasmic sperm injection cycles using donated oocytes by using testicular spermatozoa obtained by testicular sperm extraction. MATERIALS AND METHODS: This was a retrospective study of 123 couples who underwent a testicular sperm extraction‒intracytoplasmic sperm injection cycle after vasectomy using donated oocytes. Subjects were divided into groups according to time since vasectomy and the male risk factor evaluated. The main outcomes measured were live birth rate per embryo transfer, per oocyte donation cycle, and per couple. We assessed the cumulative live birth rate according to the time since vasectomy and considered male comorbidities: body mass index, hypertension, diabetes mellitus, dyslipidemia, and smoking. RESULTS: The overall live birth rate per couple was 59.3% (50.6-68.0). Considering the number of embryo transfer and oocyte donation cycle, the live birth rates were 34.1% (27.8-40.4) and 44.5% (36.9-52.1), respectively. The live birth rate according to time since vasectomy was not statistically different between groups. Consequently, the cumulative live birth rate was similar between the different interval times when considering one to eight embryo transfers (p = 0.74). No statistical differences in live birth rate and cumulative live birth rate were found between groups clustered according to male body mass index, smoking, hypertension, and dyslipidemia. However, diabetic male patients had a significantly lower rate of live birth rate per couple (22.2% [4.94-49.4]) than non-diabetic patients did (62.7% [53.7-71.8]) (p = 0.03), but not in their cumulative live birth rate. CONCLUSIONS: The time since vasectomy seems to have no detrimental effects on the live birth rate and cumulative live birth rate in testicular sperm extraction‒intracytoplasmic sperm injection cycles with donated oocytes. Male diabetes negatively affects the overall live birth rate per couple, but not the cumulative live birth rate. These results could be useful for multidisciplinary patient-tailored counseling, regarding the chance of having a pregnancy and facilitating the decision-making process of the fertility specialists.

The ovarian stimulation regimen does not affect aneuploidy or blastocyst rate.

RESEARCH QUESTION: Could the total dose (<3000 IU or ≥3000 IU) and type of exogenous gonadotrophin (i.e. recombinant FSH and/or human menopausal gonadotrophin [HMG]) influence aneuploidy and blastulation rates and produce different reproductive outcomes? DESIGN: This retrospective, observational, multicentre cohort study included a total of 8466 patients undergoing IVF using autologous oocytes and preimplantation genetic testing for aneuploidies. Participants were divided according to the dosage of total gonadotrophins and stratified by maternal age. RESULTS: The aneuploidy rates, pregnancy outcomes and cumulative live birth rates (CLBR) were similar among women who received total gonadotrophin dosages of <3000 or ≥3000 IU. No statistical differences were reported in the blastulation rate with lower or higher gonadotrophin dosages. Women receiving a higher amount of HMG during ovarian stimulation had a lower aneuploidy rate (P = 0.02); when stratified according to age, younger women with a higher HMG dosage had lower aneuploidy rates (P< 0.001), while no statistical differences were observed in older women with higher or lower HMG dosages. No significant differences were observed in IVF outcomes or CLBR. CONCLUSIONS: High doses of gonadotrophins were not associated with rate of aneuploidy. However, an increased fraction of HMG in younger women was associated with a lower aneuploidy rate. The study demonstrated that the total gonadotrophin dosage did not influence aneuploidy, reproductive outcomes or CLBR. The increased gonadotrophin and HMG dosages used for ovarian stimulation did not precede aneuploidy, and the use of HMG should be evaluated on a case-by-case basis, according to the individual's characteristics and infertility type.

Assessment of reproductive outcomes of fresh versus cryopreserved ejaculated sperm samples-a retrospective analysis of 44 423 oocyte donation ICSI cycles.

STUDY QUESTION: Does the use of frozen sperm affect live birth rate (LBR) and cumulative LBR (CLBR) compared to fresh sperm samples in oocyte donation ICSI cycles? SUMMARY ANSWER: Although there were slight decreases in pregnancy rates (PRs) and LBR, as well as CLBR per embryo replaced and per embryo transfer (ET), when frozen sperm samples were used compared to fresh ejaculates, their clinical impact was limited. WHAT IS KNOWN ALREADY: Sperm cryopreservation is part of the daily routine in reproduction clinics worldwide because of its many advantages in cycle planning. Nonetheless, there is a lack of agreement in terms of its impact on the outcomes of ICSI cycles. Previous studies showed conflicting conclusions and focused on different populations, which makes reaching consensus on the impact of sperm freezing-thawing complicated. Moreover, classical parameters are used to assess cycle success: pregnancy, live birth and miscarriage rates per ET. This study reports those measurements plus CLBR, which more accurately reflects the impact of the technique on the likelihood of achieving a newborn. STUDY DESIGN, SIZE, DURATION: A retrospective multicenter observational cohort study, including data from 37 041 couples and 44 423 ICSI procedures from January 2008 to June 2022, was carried out. The group using frozen sperm included 23 852 transferred embryos and 108 661 inseminated oocytes, whereas the fresh sample group comprised 73 953 embryos replaced and 381 509 injected oocytes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Outcomes measured per first ET and per ET were compared between groups using Fisher's exact test and Chi-squared test, as appropriate. Binary-logistics regression models were used to adjust the analyses according to clinically relevant co-variables. Kaplan-Meier curves plotted the CLBR per oocyte inseminated, per embryo replaced and per ET, and compared between groups using the Mantel-Cox test. Cox regressions were employed for the multivariate analyses of CLBR. MAIN RESULTS AND THE ROLE OF CHANCE: The frozen sperm group showed a slightly lower biochemical (3.55% and 2.56%), clinical (3.68% and 3.54%) and ongoing (3.63% and 3.15%) PR compared to the cycles using fresh sperm, respectively, both per first ET and per ET. LBR was 4.57% lower per first ET and 3.95% lower per ET in the frozen sperm group than the fresh sperm group. There was also a subtle increase of 2.66% in biochemical miscarriage rate per ET when using frozen versus fresh sperm. All these differences remained statistically significant after the multivariate analysis (adjusted P ≤ 0.001). There were statistically significant differences in CLBR per embryo replaced and per ET but not per oocyte used (adjusted P = 0.071). Despite the statistical significance of the differences between the groups, those using frozen sperm required only 0.54 more oocytes injected, 0.45 more embryos transferred and 0.41 more ET procedures, on average, to achieve a live birth compared to the fresh samples. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study subjects the data to biases or potential errors during annotation on the source clinical and cycle records. This study uses multivariate analyses to control biases as much as possible. Using the oocyte donation model also contributes to reducing heterogeneity in the oocyte quality factor. WIDER IMPLICATIONS OF THE FINDINGS: The large sample sizes included in this study allowed for the detection of small changes in cycle success rates between groups. Although statistically significant, the decrease in PRs, LBR, and CLBR when using frozen sperm can be clinically overlooked in favor of the many benefits of sperm cryopreservation. STUDY FUNDING/COMPETING INTEREST(S): None declared. TRIAL REGISTRATION NUMBER: Not applicable.

Elevated Sperm DNA Damage in IVF-ICSI Treatments Is Not Related to Pregnancy Complications and Adverse Neonatal Outcomes.

This multicenter retrospective cohort study assesses the effect of high paternal DNA fragmentation on the well-being of the woman during pregnancy and the health of the newborn delivered. It was performed with clinical data from 488 couples who had a delivery of at least one newborn between January 2000 and March 2019 (243 used autologous oocytes and 245 utilized donated oocytes). Couples were categorized according to sperm DNA fragmentation (SDF) level as ≤15% or >15%, measured by TUNEL assay. Pregnancy, delivery, and neonatal outcomes were assessed. In singleton pregnancies from autologous cycles, a higher but non-significant incidence of pre-eclampsia, threatened preterm labor, and premature rupture of membranes was found in pregnant women from the >15%SDF group. Additionally, a higher proportion of children were born with low birth weight, although the difference was not statistically significant. After adjusting for potential confounders, these couples had lower odds of having a female neonate (AOR = 0.35 (0.1-0.9), p = 0.04). Regarding couples using donor's oocytes, pregnancy and neonatal outcomes were comparable between groups, although the incidence of induced vaginal labor was significantly higher in the >15% SDF group (OR = 7.4 (1.2-46.7), p = 0.02). Adjusted analysis revealed no significant association of elevated SDF with adverse events. In multiple deliveries from cycles using both types of oocytes, the obstetric and neonatal outcomes were found to be similar between groups. In conclusion, the presence of an elevated SDF does not contribute to the occurrence of clinically relevant adverse maternal events during pregnancies, nor does it increase the risk of worse neonatal outcomes in newborns. Nevertheless, a higher SDF seems to be related to a higher ratio of male livebirths.

Obstetrical and Perinatal Outcomes Are Not Associated with Advanced Paternal Age in IVF or ICSI Pregnancies with Autologous Oocytes.

BACKGROUND: In recent years, there has been an evident delay in childbearing and concerns have been raised about whether this increase in age affects reproductive outcomes. This study aimed to evaluate the effect of paternal age on obstetrical and perinatal outcomes in couples undergoing in vitro fertilization or intracytoplasmic sperm injection using autologous sperm and oocytes. METHODS: This retrospective study evaluated obstetrical and perinatal outcomes from 14,125 couples that were arbitrarily divided into three groups according to paternal age at conception: ≤30 (n = 1164), 31-40 (n = 11,668) and >40 (n = 1293). Statistics consisted of a descriptive analysis followed by univariate and multivariate models, using the youngest age group as a reference. RESULTS: The study showed significantly longer pregnancies for the fathers aged 31-40 compared to ≤30 years. However, there were no significant differences for the type of delivery, gestational diabetes, anaemia, hypertension, delivery threat, premature rupture of membranes, preterm birth, very preterm birth, and the neonate's sex, weight, low birth weight, very low birth weight, length, cranial perimeter, Apgar score and neonatal intensive care unit admission. CONCLUSION: Despite our promising results for older fathers, as paternal age was not associated with clinically relevant obstetrical and perinatal outcomes, future well-designed studies are necessary as it has been associated with other important disorders.

Semen processing using magnetic-activated cell sorting before ICSI is deemed safe for obstetric and perinatal outcomes: a retrospective multicentre study.

RESEARCH QUESTION: Is magnetic-activated cell sorting (MACS) a safe semen sample processing technique for newborns and mothers when used for semen processing prior to intracytoplasmic sperm injection (ICSI) cycles? DESIGN: This retrospective multicentre cohort study involved patients undergoing ICSI cycles with either donor or autologous oocytes from January 2008 to February 2020. They were divided into two groups: those who underwent standard semen preparation (reference group) and those who had an added MACS procedure (MACS group). A total of 25,356 deliveries were assessed in the case of cycles using donor oocytes, and 19,703 deliveries from cycles using autologous oocytes. Of these, 20,439 and 15,917, respectively, were singleton deliveries. Obstetric and perinatal outcomes were retrospectively assessed. All means, rates and incidences were computed per live newborn in each study group. RESULTS: There were no significant differences between the main obstetric and perinatal morbidities affecting the mothers' and newborns' well-being between groups using either donated or autologous oocytes. There was a significant increase in the incidence of gestational anaemia in both subpopulations (donor oocytes P = 0.01; autologous oocytes P < 0.001). However, this incidence was within the estimated prevalence for gestational anaemia in the general population. There was a statistically significant decrease in preterm (P = 0.02) and very preterm (P = 0.01) birth rates in the MACS group in cycles using donor oocytes. CONCLUSIONS: The use of MACS during semen preparation before ICSI using either donor or autologous oocytes appears to be safe for the mothers' and newborns' well-being during pregnancy and birth. Nevertheless, a close follow-up of these parameters in the future is advised, especially concerning anaemia, in order to detect even smaller effect sizes.

Advanced Paternal Age Does Not Affect Medically-Relevant Obstetrical and Perinatal Outcomes following IVF or ICSI in Humans with Donated Oocytes.

BACKGROUND: Concomitant with delays in childbearing, concerns have been raised of whether advanced paternal age is associated with adverse reproductive outcomes, but the evidence is controversial in part due to the uncertain threshold in which to consider advanced paternal age and confounding maternal factors. This retrospective study aimed to evaluate the effect of paternal age on reproductive outcomes related to the pregnancy and perinatal health of the offspring. METHODS: We retrospectively evaluated 16,268 cases of patients who underwent IVF or ICSI (using autologous sperm and donated oocytes, between January 2008 and March 2020, at Spanish IVIRMA clinics. Patients were divided based on paternal age at conception [≤30 (n = 204), 31-40 (n = 5752), and >40 years (n = 10,312)], and the differences in obstetrical and perinatal outcomes were analyzed by descriptive analysis, followed by univariate and multivariate analysis. RESULTS: Fathers 31-40 and >40 years old were associated with lower odds of caesarean delivery [AOR 0.63 (95% CI, 0.44-0.90; p = 0.012) and AOR 0.61 (95% CI, 0.41-0.91; p = 0.017), respectively] and longer pregnancies [ARC 5.09 (95% CI, 2.39-7.79; p < 0.001) and ARC 4.54 (95% CI, 1.51-7.58; p = 0.003), respectively] with respect to fathers ≤30 years old. Furthermore, fathers aged 31-40 years old had lower odds of having a female infant (AOR, 0.70; 95% CI, 0.49-0.99; p = 0.045) than those ≤30. The rest of obstetrical and perinatal outcomes, which we deemed more medically-relevant as they were considered serious for health, were comparable between groups with our adjusted model. CONCLUSIONS: Despite this hopeful message to fathers of advanced paternal age, future studies should consider the short- and long-term outcomes of the offspring and try to better elucidate the associations of advanced paternal age with reproductive outcomes and the molecular mechanisms underlying the observed associations.

Switching to testicular sperm after a previous ICSI failure with ejaculated sperm significantly improves blastocyst quality without increasing aneuploidy risk.

PURPOSE: The use of testicular sperm is confined to patients with azoospermia, but there is evidence to support its use in males with poor semen parameters and/or previous intracytoplasmic sperm injection (ICSI) failures with ejaculated spermatozoa. We compared the aneuploidy rate and quality between embryos derived from ICSI cycles with ejaculated sperm (EJ-ICSI) and those from ICSI cycles using testicular spermatozoa (TT-ICSI) within the same couple. METHODS: Retrospective study of 27 couples who first underwent an EJ-ICSI cycle that did not result in a livebirth and afterwards a TT-ICSI cycle. Only the two closer cycles of each couple were included. Preimplantation genetic test for aneuploidies (PGT-A) was performed in both ICSI cycles and classic parameters of embryo quality were assessed until blastocyst-stage. RESULTS: A total of 375 embryos from 54 ICSI cycles were evaluated. Aneuploidy rate was measured by two different parameters. Patients undergoing TT-ICSI presented a similar aneuploidy rate as EJ-ICSI group: 30.7% (23.4-38.0) vs 26.8% (18.1-35.5) per inseminated oocytes (P>0.05), and 76.2% (66.2-86.2) vs 72.1% (59.1-85.2) per the total number of biopsied embryos (P>0.05), respectively. Further, the good-quality blastocyst rate per correctly fertilized oocyte was significantly higher in TT-ICSI group (33.6% (30.4-36.9)) than EJ-ICSI group (24.2% (20.3-28.0)) (P<0.001). CONCLUSIONS: Switching to testicular sperm for ICSI yielded better-quality blastocysts without affecting the chromosomal load of the embryos in non-azoospermic couples with a previous unsuccessful ICSI using ejaculated sperm. This strategy is a good option for couples seeking a livebirth who do not want to use donor sperm.