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OBJECTIVE: To study whether severe male factor infertility (SMF), reflected by oligozoospermia, impacts embryo morphokinetic behavior in low-prognosis women as stratified by the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria. DESIGN: Cohort study. SETTING: Private university-affiliated in vitro fertilization center. PATIENT(S): A total of 10,366 injected oocytes from 2,272 women who underwent intracytoplasmic sperm injection cycles between March 2019 and April 2022. INTERVENTION(S): Patients were divided into 8 groups according to the POSEIDON criteria (1-4) and the presence or absence of SMF. A control group of normoresponder patients was included. Kinetic markers from the point of insemination were recorded in the EmbryoScope incubator. MAIN OUTCOME MEASURE(S): Morphokinetic milestones and intracytoplasmic sperm injection clinical outcomes. RESULT(S): Embryos from patients in the POSEIDON 1 group showed significantly slower timing to pronuclear appearance, timing to pronuclear fading (tPNf), timing to 2 (t2), 3 (t3), 4 (t4), 6 (t6), and 7 (t7) cells than those from the control group. Known Implantation Diagnosis Score ranking was significantly different between the SMF and non-SMF (nSMF) subgroups in both POSEIDON 1 as well as control groups. Embryos from patients in the POSEIDON 2 group showed significantly slower timing to pronuclear appearance, t4, t6, t7, timing to 8 cells (t8), and timing to morulae than those from the control group. Embryos in the POSEIDON 2 SMF subgroup took longer than those in the POSEIDON 2 nSMF subgroup and those in both control subgroups to achieve tPNf, t2, t3, timing to 5 cells (t5), timing to start blastulation, and timing to blastulation. Known Implantation Diagnosis Score ranking was significantly different between the SMF and nSMF subgroups in both POSEIDON 2 as well as control groups. Embryos from patients in the POSEIDON 3 group showed significantly slower t8 and duration of the second cell cycle (t3-t2) than those from the control group. Known Implantation Diagnosis Score ranking was significantly different across the subgroups. Embryos derived from patients in the POSEIDON 4 group showed significantly slower tPNf, t2, t3, t4, t5, t6, t7, t8, timing to complete t4-t3 synchronous divisions, and timing to complete t8-t5 synchronous divisions than those from the control group. Known Implantation Diagnosis Score ranking was significantly different between the SMF and nSMF subgroups in both POSEIDON 4 as well as control groups. Irrespective of sperm quality, clinical outcomes significantly improved in the control subgroups compared with those in the POSEIDON 2 and 4 subgroups. CONCLUSION(S): Embryos in the SMF groups presented lower Known Implantation Diagnosis Score ranking than those in the nSMF groups in both POSEIDON 1-4 and control groups, suggesting that cumulative differences result in worse morphokinetic development when the algorithm is used.

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The objective of this study was to investigate the impact of sperm source on embryo morphokinetics and the clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles by considering the clustering of data (multiple embryos per patient that share a comparable developmental timing). This matched cohort study was performed at a private university-affiliated in vitro fertilization center. Women who underwent ICSI with epididymal sperm between January 2019 and December 2020 (the percutaneous epididymal sperm aspiration group, n = 32 cycles) were matched with women who underwent ICSI with ejaculated sperm because of idiopathic male factor infertility (the male factor infertility [MFI] group, n = 32 cycles) or female infertility (the control group, n = 32 cycles). Embryos were cultured in a time-lapse imaging incubator, and morphokinetic development was recorded and compared among the groups. Significantly slower divisions were observed in embryos derived from epididymal sperm than in those derived from the MFI and control groups. Embryos derived from epididymal sperm had a significantly lower KIDScore (3.1 ± 0.2) than did those derived from ejaculated spermatozoa from the MFI (5.4 ± 0.1) and control (5.6 ± 0.2, p < 0.001) groups. Epididymal sperm-derived embryos showed a significantly greater occurrence of multinucleation (23.2%) than did those derived from ejaculated sperm from the MFI and control groups (2.8% and 3.7%, p < 0.001, respectively). Epididymal sperm-derived embryos were significantly more likely to undergo direct or reverse cleavage (11.1%) than ejaculated sperm-derived embryos in the control group (4.3%, p = 0.001). In conclusion, delayed cell cleavage and increased incidences of blastomere multinucleation and abnormal cleavage patterns are observed when epididymal-derived sperm are used for ICSI.

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Background: In Brazil, donor anonymity is mandatory; however, the tendency of Brazilians towards the practice is unknown. In this study, an attempt was made to investigate whether couples undergoing assisted reproductive technology (ART) have a different perception of anonymous versus identity-release gamete donation than a target population in Brazil. Methods: This cross-sectional study was performed from September 1, 2020 to December 15, 2020. For that purpose, surveys through online platforms were conducted, including either patients undergoing ART (ART-group, n=400) or subjects interested in the theme (interested-group, n=100) randomized by age at a 1:4 ratio. The survey collected information on the participants' attitudes towards anonymity of gamete donors, and answers were compared between the groups. Results: Most participants stated that the relationship between children and their parents would be affected by the child's knowledge of the origin of its conception. Most participants in the ART-group believed that the gamete donor's identity should not be revealed to the child, while only half of the interested-group stated the same. Most of the participants stated that "the donor's identity should be revealed if the child questions its biological origin". "From birth" was the second most common response, while "when the child turns 18 years old" and "sometime during teenage years" were less common answers. Conclusion: The attitudes of ART patients about anonymity are conservative, with most participants believing that family relationships may be affected if the child is aware of the origin of his/her conception. These patients also believe that the identity of the gamete donor should not be revealed to the child.

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The goal for the present study was to investigate the effect of aneuploidy on embryo morphokinetics events in a time-lapse imaging (TLI) system incubator. This retrospective cohort study was performed in a private university-affiliated in vitro fertilization center, between 2019 March and December 2020. Kinetic data were analyzed in 935 embryos, derived from 316 patients undergoing intracytoplasmic sperm injection cycle with preimplantation genetic testing (PGT) for aneuploidy, individually cultured in a TLI incubator until Day 5 of development. Timing of morphokinetic variables, the incidences of multinucleation, and Known Implantation Data Score (KIDScore)-Day 5 were compared between euploid (n = 352) and aneuploid embryos (n = 583). Aneuploid embryos showed significantly longer timing to complete specific morphokinetic parameters compared to euploidy embryos. Euploidy embryos also showed a significantly higher KIDScore when compared with the aneuploidy ones. Our evidence suggests that TLI monitoring may be an adjunct approach to select embryos for PGT; however, cautious investigation is still needed.

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BACKGROUND: Sperm deoxyribonucleic acid (DNA) fragmentation is commonly encountered in spermatozoa, and the oocyte assumes responsibility for repairing sperm DNA fragmentation during the oocyte-embryo transition. OBJECTIVES: This study aimed to investigate whether the effect of sperm DNA fragmentation on intracytoplasmic sperm injection outcomes depends on the incidence of oocyte dimorphisms. MATERIALS AND METHODS: For the present cohort, 2942 fertilized oocytes from 525 patients submitted to intracytoplasmic sperm injection cycles were assessed. The present study was conducted in a private in vitro fertilization center affiliated to a university from June 2016 to July 2019. Semen samples were divided into the following two groups depending on the sperm DNA fragmentation index: a low fragmentation index group (<30% sperm DNA fragmentation, n = 1468) and a high fragmentation index group (≥30% sperm DNA fragmentation, n = 486). In addition, mature oocytes were examined before sperm injection, and intracytoplasmic and extracytoplasmic defects were recorded. The effect of the sperm DNA fragmentation index on laboratory and clinical intracytoplasmic sperm injection outcomes (depending on the presence of oocyte defects) was evaluated. RESULTS: Significant increases in the rates of fertilization, high-quality embryo, implantation, and pregnancy were noted for cycles with <30% sperm DNA fragmentation than cycles with ≥30% sperm DNA fragmentation (regardless of the presence of oocyte dimorphisms). The presence of dimorphisms significantly impacted laboratory and clinical outcomes. The lowest fertilization and high-quality embryo rates were observed when a high sperm DNA fragmentation index was associated with the presence of dark cytoplasm, vacuoles, resistant membrane, and non-resistant membrane. The lowest implantation and pregnancy rates were observed when a high sperm DNA fragmentation index was associated with the presence of vacuoles, defective perivitelline space, and fragmented polar body. The effect of sperm DNA fragmentation on miscarriage rates was significantly influenced by the presence of centrally located cytoplasmic granulation, a defective perivitelline space and non-resistant membrane. CONCLUSION: A high sperm DNA fragmentation index increases the likelihood of miscarriage in intracytoplasmic sperm injection cycles, an effect that may potentially be magnified by the presence of oocyte dysmorphisms.

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The goal for the present study was to investigate whether previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may compromise embryo morphokinetics and implantation. For that, a historical cohort study was performed in a private university-affiliated in vitro fertilization center. The study included 1628 embryos from 88 patients undergoing intracytoplasmic sperm injection (ICSI) cycles. Patients were age-matched in a 1:3 ratio to either a coronavirus disease (COVID) group, including patients with a positive SARS-CoV-2 immunoglobulin test (n = 22 patients, 386 embryos), or a control group, including patients with a negative SARS-CoV-2 immunoglobulin test (n = 66, 1242 embryos). The effect of previous infection with SARS-CoV-2 on morphokinetic events and ICSI outcomes was evaluated. Embryos derived from patients in the COVID group presented longer time to pronuclei appearance and fading, time to form two, three, four and five cells, and time to blastulation. The durations of the third cell cycle and to time to complete synchronous divisions were also significantly increased in the COVID group compared with the control group, whereas known implantation diagnosis score Day 5 ranked significantly lower in the COVID group. No differences were observed between the COVID and control groups on clinical outcomes. In conclusion, patients planning parenthood, who have recovered from COVID-19 infection, must be aware of a possible effect of the infection on embryo development potential.

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OBJECTIVE: To investigate whether the timing of rLH addition to rFSH during controlled ovarian stimulation (COS) impacts ovarian response and the outcomes of intracytoplasmic sperm injection (ICSI) cycles. METHODS: Data of 1278 patients undergoing ICSI between 2015 and 2018, in a private university-affiliated IVF center were analyzed. Patients were divided into groups according to the timing of LH addition to the COS protocol: Group LH-start (n=323), in which LH was administered since day 1 of ovarian stimulation; and Group LH-mid (n=955), in which LH was administered concomitantly with gonadotropin releasing hormone (GnRH) antagonist. Data were also stratified according to female age and response to COS. The outcomes of COS and ICSI were compared between the groups. RESULTS: For the general group and in patients aged ≥ 35 years, higher blastocyst development rates were in Group LH-mid compared to Group LH-start. In patients with poor response to COS (POR), higher fertilization rate, blastocyst development rate and implantation rate were observed in Group LH-mid. CONCLUSIONS: rLH supplementation in POR patients may improve laboratorial and clinical outcomes when started in the mid-follicular phase, in GnRH antagonist ICSI cycles.

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The objective of this cross-sectional study was to investigate the impact of paternal age on the outcomes of intracytoplasmic sperm injection (ICSI) cycles at different values of maternal age. A total of 21,960 injected oocytes deriving from 3837 ICSI cycles performed between January 2014 and October 2020, performed in a private university-affiliated in vitro fertilization centre was included. The main effects of maternal and paternal age, as well as the effect of their product (interaction term) on embryo development and pregnancy outcomes were investigated considering the clustering of data. The coefficients for the interaction term were statistically significant for blastocyst development, top-quality blastocyst, implantation, pregnancy, miscarriage, and live-birth rates. For every 1-year increase in paternal age, the odds ratio of live-birth reduces by 1% in females aged 37 years, 1.6% in those aged 38 years, 2.4% in 39-year-old females, 5% in 42-year-old females and so on. An increase in the interaction term by 1 year decreases the pregnancy rate by 0.4% and live-birth rate by 0.8 and increases the miscarriage rate by 1.2%. The slopes of maternal age on blastulation, blastocyst quality, and implantation, pregnancy, miscarriage, and live-birth rate significantly changed (worsened) for every year increase in paternal age.

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OBJECTIVE: To evaluate if ovarian response to controlled ovarian stimulation (COS) and intracytoplasmic sperm injection (ICSI) outcomes are improved by the use of dual trigger (gonadotropin-releasing hormone (GnRH) agonists plus recombinant human chorionic gonadotropin (r-hCG)) in patients with previous cycles triggered with r-hCG. METHODS: This case-control study included 88 matched cycles performed in 88 patients, which had the first ICSI cycle triggered with r-hCG (n=44), and the following ICSI cycle with dual trigger (n=44). We compared the cycle outcomes between the groups. In a second case-control within-subject analyses, we compared the ICSI outcomes between patients which had the first ICSI cycle triggered with r-hCG only (n=18), and the following ICSI cycle with dual trigger (n=18) or r-hCG only (n=18). RESULTS: Upon investigating repeated cycles (r-hCG only vs. dual trigger), we found higher oocyte yield and mature oocyte rates, lower immature oocyte rates, higher fertilization rates, and higher blastocyst development rates; and higher rates of cycles with embryos transferred and implantation in the dual trigger cycle. CONCLUSIONS: The dual trigger regimen is a more effective approach than r-hCG trigger in patients with a previous r-hCG triggered ICSI cycle, yielding improved response to COS, and better laboratorial and clinical outcomes.

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OBJECTIVE: To investigate whether patients with a previous recombinant follicle stimulating hormone (rFSH)-stimulated cycle would have improved outcomes with rFSH + recombinant luteinizing hormone (rLH) stimulation in the following cycle. METHODS: For the present retrospective case-control study, 228 cycles performed in 114 patients undergoing intracytoplasmic sperm injection (ICSI) between 2015 and 2018 in an in vitro fertilization (IVF) center were evaluated. Controlled ovarian stimulation (COS) was achieved with rFSH (Gonal-f, Serono, Geneva, Switzerland) in the first ICSI cycle (rFSH group), and with rFSH and rLH (Pergoveris, Merck Serono S.p.A, Bari, Italy) in the second cycle (rFSH + rLH group). The ICSI outcomes were compared among the groups. RESULTS: Higher estradiol levels, oocyte yield, day-3 high-quality embryos rate and implantation rate, and a lower miscarriage rate were observed in the rFSH + rLH group compared with the rFSH group. In patients < 35 years old, the implantation rate was higher in the rFSH + rLH group compared with the rFSH group. In patients ≥ 35 years old, higher estradiol levels, oocyte yield, day-3 high-quality embryos rate, and implantation rate were observed in the rFSH + rLH group. In patients with ≤ 4 retrieved oocytes, oocyte yield, mature oocytes rate, normal cleavage speed, implantation rate, and miscarriage rate were improved in the rFSH + rLH group. In patients with ≥ 5 retrieved oocytes, higher estradiol levels, oocyte yield, and implantation rate were observed in the rFSH + rLH group. CONCLUSION: Ovarian stimulation with luteinizing hormone (LH) supplementation results in higher implantation rates, independent of maternal age and response to COS when compared with previous cycles stimulated with rFSH only. Improvements were also observed for ICSI outcomes and miscarriage after stratification by age and retrieved oocytes.

OBJETIVO: Investigar se há algum efeito da suplementação com hormônio luteinizante (LH, na sigla em inglês) no regime com antagonista do hormônio liberador de gonadotropina (GnRH, na sigla em inglês) sobre os resultados dos ciclos consecutivos de injeção intracitoplasmática de espermatozoides (ICSI, na sigla em inglês). MéTODOS: Para o presente estudo retrospectivo de caso-controle, foram avaliados 228 ciclos de microinjeção intracitoplasmática de espermatozoides (ICSI, na sigla em inglês) realizados em 114 pacientes entre 2015 e 2018 em um centro privado de fertilização in vitro (FIV) afiliado a uma universidade. O estímulo ovariano controlado (EOC) foi feito com hormônio folículo- estimulante recombinante (rFSH, na sigla em inglês) (Gonal-f, Serono, Genebra, Suíça) no primeiro ciclo de ICSI (grupo rFSH), e com rFSH e rLH (Pergoveris, Merck Serono S.p.A, Bari, Itália) no segundo ciclo (grupo rFSH + rLH). Os desfechos dos ciclos de ICSI foram comparados entre os grupos. RESULTADOS: Níveis mais elevados de estradiol, de recuperação oocitária, taxa de embriões de alta qualidade no 3° dia e taxa de implantação, e menor taxa de aborto foram observados no grupo rFSH + rLH. Em pacientes < 35 anos, a taxa de implantação foi maior no grupo rFSH + rLH em comparação com o grupo rFSH. Em pacientes com ≥ 35 anos, maiores níveis de estradiol, recuperação oocitária, a taxa de embriões de alta qualidade no 3° dia e a taxa de implantação foram observados no grupo rFSH + rLH. Em pacientes com baixa resposta ao EOC (≤ 4 oócitos recuperados), a recuperação oocitária, a taxa de oócitos maduros, a taxa de velocidade normal de clivagem, a taxa de implantação e a taxa de aborto foram melhoradas no grupo rFSH + rLH. Em pacientes com resposta normal ao EOC (≥ 5 oócitos recuperados), níveis mais elevados de estradiol, recuperação oocitária e taxa de implantação foram observados no grupo rFSH + rLH. CONCLUSãO: A estimulação ovariana com suplementação de LH resultou em taxas de implantação mais altas, independentemente da idade materna e da resposta ao EOC, em comparação com os ciclos anteriores estimulados apenas com rFSH. Melhorias também foram observadas nos resultados da ICSI e na taxa de aborto quando as pacientes foram estratificadas por idade e número de oócitos recuperados.

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The objective of this study was to investigate the impact of male age, semen quality and days of ejaculatory abstinence on embryo morphokinetics. A total of 1,220 zygotes obtained from 139 couples in a private in vitro fertilisation centre were analysed. The timing of specific events from the point of insemination, such as timings to pronuclei appearance and fading, to two, three, four, five, six, seven and eight cells and to blastulation were recorded. Multivariate linear regression analysis was used to evaluate the influence of paternal factors on embryo morphokinetic events. Paternal age was positively correlated with delayed cell cleavage and blastulation, and negatively associated with implantation rate, and clinical pregnancy and live-birth chances. The ejaculatory abstinence was inversely correlated with the implantation rate. Inverse relationships were observed between semen parameters (sperm count, progressive sperm motility, total motile sperm count and morphology) and the timing of specific events during embryo development. Sperm morphology was also positively associated with implantation rate and pregnancy and live-birth chances. Increased paternal age and ejaculatory abstinence, and poor semen quality correlate with delayed cell cleavage and blastulation and negatively impact intracytoplasmic sperm injection outcomes.

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BACKGROUND: Coronavirus disease 2019 (COVID-19), which causes serious respiratory illnesses such as pneumonia and lung failure, was first reported in mid-December 2019 in China and has spread around the world. In addition to causing serious respiratory illnesses such as pneumonia and lung failure, there have been conflicting reports about the presence of SARS-CoV-2 in the semen of patients who were previously diagnosed with COVID-19 and possible implications for the male reproductive tract. OBJECTIVE: The goal for the present study was to review the current status of the literature concerning COVID-19 and male reproduction. MATERIAL AND METHODS: An electronic literature search was done by using PubMed and Google Scholar databases. Relevant papers, concerning SARS-COV-2 and COVID-19 and male reproduction, published between January 2020 and December 2020 were selected, analyzed and eventually included in the present literature review. RESULTS: SARS-CoV-2 may infect any cell type expressing angiotensin-converting enzyme 2 (ACE2), including reproductive cells. Besides the presence of the SARS-CoV-2 receptor, the expression of host proteases, such as transmembrane serine protease 2 (TMPRSS2), is needed to cleave the viral S protein, allowing permanent fusion of the viral and host cell membranes. Here, we aimed to review the current status of the literature concerning COVID-19 and male reproduction. The lack of co-expression of ACE2 and TMPRSS2 in the testis suggests that sperm cells may not be at increased risk of viral entry and spread. However, the presence of orchitis in COVID-19-confirmed patients and compromised sex-related hormonal balance among these patients intrigues reproductive medicine. DISCUSSION: SARS-CoV-2 may use alternate receptors to enter certain cell types, or the expression of ACE2 and TMPRSS2 may not be detected in healthy individuals. CONCLUSION: COVID-19 challenges all medical areas, including reproductive medicine. It is not yet clear what effects, if any, the COVID-19 pandemic will have on male reproduction. Further research is needed to understand the long-term impact of SARS-CoV-2 on male reproductive function.

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The objective of this study was to investigate any effect of cryopreservation of donated eggs on laboratorial and clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles. This retrospective cohort study included 320 oocyte recipients undergoing 307 vitrified and 119 fresh oocyte recipient ICSI cycles, participating in an egg-sharing donation programme, from 2015 to 2018, in a private university-affiliated in vitro fertilization (IVF) centre. A review of donor and recipient ICSI cycles was charted. A general mixed models fit by restricted maximum likelihood, followed by Bonferroni post hoc test was used to compare the means between fresh and warm oocyte donation groups and investigate the effect of cryopreservation on recipient ICSI outcome. The main outcome measure was blastocyst development rates. Fertilization rate, high-quality embryo rates on days 2 and 3, normal cleavage speed rates on days 2 and 3, and blastocyst development rate were significantly higher for the fresh oocyte donation cycles compared with warmed oocyte donation cycles. In the egg-sharing donation programme, fertilization and embryo developmental competence were reduced when vitrified oocytes from infertile couples were used for ICSI compared with fresh oocytes.

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OBJECTIVE: To investigate the predictive factors for successful pregnancy in oocyte recipient ICSI cycles in an egg-sharing donation program. METHODS: Analysed data were obtained via chart review of 1505 vitrified oocytes donated from 268 patients to 225 oocyte recipients, undergoing 307 ICSI cycles. Patients were participating in an egg-sharing donation program between January 2015 and May 2017. Adjusted generalised linear models were used to investigate the impact of oocyte donor and recipient characteristics on recipients' pregnancy achievement. RESULTS: Implantation rate in the oocyte donor was highly correlated with pregnancy achievement in the oocyte recipient's cycles (ExpB: 1.181, CI: 1.138-1.226, p<0.001). The ROC curve analysis demonstrated that the implantation rate in the oocyte donor has a strong predictive value for pregnancy success in the oocyte recipient (area under the curve: 0.98, CI: 0.95-0.99, p<0.001). Pregnancy in oocyte donors and recipients were highly associated (ExpB: 54.6, CI: 28.1-105.8, p<0.001), regardless of the oocyte recipient's age. In oocyte recipients, the high-quality embryos rates on days 2 (ExpB: 3.397, CI: 1.635-7.054, p=0.001) and 3 (ExpB: 6.629, CI: 1.185-37.092, p=0.031), and blastocyst development rates (ExpB: 2.331, CI: 1.086-5.001, p=0.030) were positively associated with pregnancy outcome. CONCLUSION: The strong association in pregnancy success between donors and recipients, and the lack of correlation between donor characteristics and cycles' outcomes, demonstrate the power of oocyte quality on the success of ICSI treatment.

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OBJECTIVE: To identify potential microRNA (miRNA) biomarkers of poor, normal and hyperresponse to controlled ovarian stimulation (COS). METHODS: In the present study, we assessed 40 serum samples from patients undergoing COS. We used ten samples to standardize miRNAs detection in the serum. The remaining 30 samples were split into three groups depending on the patient's response to COS: poor response (PR group, n=10), normal response (NR group, n=10), and hyperresponse (HR group, n=10). Aberrantly expressed miRNAs were identified using a large-scale expression analysis platform. Gene set enrichment analysis was performed to assess the biological processes potentially modulated by the identified miRNAs. RESULTS: Twenty-two miRNAs were detected only in the PR or HR groups when compared with the NR group. From those, 11 presented poor dissociation curves and were excluded from further analysis. A bioinformatics analysis revealed that the selected 11 miRNAs target several genes involved in GnRH, estrogen and prolactin signaling, oocyte maturation, female pregnancy, and meiosis. CONCLUSION: The large-scale analysis of miRNA expression identified distinct miRNA profiles for poor and hyperresponse to COS, which potentially modulate key processes for human assisted reproduction. All evidence suggests that the serum microRNA profiling may discriminate patients who will respond in an exacerbated manner from those who will respond insufficiently to COS. Further studies may validate these miRNAs, enabling the individualization of treatment and more successful outcomes.

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OBJECTIVE: To compare the effect of pituitary suppression regimens on oocyte morphology in consecutive ICSI cycles of the same patients. METHODS: Data was obtained from 200 matched consecutive intracytoplasmic sperm injection (ICSI) cycles performed in 100 couples undergoing the first cycle with the GnRH agonist and the following cycle with the GnRH antagonist regimen, from January 2010 to August 2016, in a private university-affiliated IVF centre. The effects of the pituitary suppression type on oocyte morphology were assessed by multivariate General Linear Models. RESULTS: Mean interval between cycles was 185.32±192.85 days. Maternal age, body mass index, and total FSH dose administered were similar in both patients' cycles. Antagonist cycles presented lower incidence of dark cytoplasm (0.69±3.28% vs. 4.40±17.70%, p=0.047), Smooth endoplasmic reticulum (SER cluster (4.37±11.62% vs. 7.36±17.17%, p=0.046), and ZP defects (6.05±14.76% vs. 11.84±25.13%, p=0.049). Similar numbers of follicles retrieved oocytes, and mature oocytes were observed between the GnRH groups, as well as the fertilisation rate, number of obtained embryos, high-quality embryo rates, and the clinical outcomes. CONCLUSION: GnRH antagonist's inhibitory effect on the ovaries in consecutive ICSI cycles results in improved oocyte maturity and morphology, despite similar laboratory and clinical outcomes, compared to the GnRH agonist treatment.

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The couple from this clinical case consisted of a 55 years old male with an obstructive interval of 25 years post vasectomy, and a 38 years old female partner. Both partners had normal results in infertility workup. Five mature oocytes were injected with motile spermatozoa showing morphological alterations, obtained by percutaneous epididymal sperm aspiration. Four oocytes fertilized, and three embryos were transferred with assisted hatching on day three of development, of which one was a high-quality embryo. A clinical pregnancy was confirmed by the detection of two gestational sacs with foetal heartbeats. Pregnancy was ongoing during the submission of this manuscript. The use of ICSI with PESA/TESA should be considered as a feasible alternative when vasectomy reversal fails in vasectomized men wishing to father again. Case reports like this may inspire the counseling of couples that have suffered from a previous vasectomy reversal failure and support the recommendation of ICSI with PESA treatment, which could allow those couples to have their own children, even in the presence of advanced parental age.

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OBJECTIVE: The aim of this study was to investigate which factors contribute to the incidence of immature oocytes (germinal vesicle -GV- and metaphase I -MI-) and how they impact the intracytoplasmic sperm injection (ICSI) outcomes of sibling mature oocytes. METHODS: Data from 3,920 cycles performed from June/2010 to August/2016 in a private university-affiliated IVF center were evaluated for the influence of controlled ovarian stimulation protocol (COS) on immature oocytes incidence and its effects on ICSI outcomes. RESULTS: MI (p=0.004) and GV (p=0.029) number were negatively correlated with gonadotropin dose. Patients stimulated by rFSH had increased GV/oocyte rate in both GnRH agonists (p<0.001) and antagonist (p=0.042) protocols, in comparison to rFSH associated with rLH protocol. MI and GV/oocyte rates were negatively correlated to fertilization (p<0.001), high-quality embryo on da p<0.001; GV/oocyte p=0.033) and pregnancy (MI/oocyte p=0.002; GV/oocyte p=0.013) rates. Cycles above a 10.5% MI/oocyte cut-off were correlated to higher response to ovarian stimulation, poor embryo development and almost two times lower pregnancy rate. Immature oocyte incidence is affected by COS and impacts on ICSI outcomes. CONCLUSION: Our evidence suggests that oocytes derived from a cohort with high incidence of maturation fail may have detrimental clinical outcomes.

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OBJECTIVE: This study aimed to look into the use of serum metabolites as potential biomarkers of response to controlled ovarian stimulation (COS) in patients undergoing intracytoplasmic sperm injection (ICSI) cycles. METHODS: This case-control study analyzed serum samples from 30 patients aged <36 years undergoing COS for ICSI in a university-affiliated assisted reproduction center from January 2017 to August 2017. The samples were split into three groups based on response to COS as follows: poor responders: <4 retrieved oocytes (PR group, n=10); normal responders: ≥ 8 and ≤ 12 retrieved oocytes (NR group, n=10); and hyper-responders: >25 retrieved oocytes (HR, n=10). The metabolic profiles of the serum samples were compared between the groups through Principal Component Analysis (PCA). Receiver Operating Characteristic (ROC) curves were built to assess the power of the model at predicting response to COS. RESULTS: PCA clearly distinguished between PR, NR and HR, and 10 ions were chosen as potential biomarkers of response to COS. These ions were more specific for PR than for NR. The ROC curve considering PR and NR had an area under the curve of 99.6% (95% CI: 88.9 - 100%). CONCLUSION: The preliminary evidence discussed in this study suggests that serum metabolites may be used as predictive molecular markers of ovarian response to controlled stimulation. The integration of clinical and "omics" findings may allow the migration toward an era of personalized treatment in reproductive medicine.

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OBJECTIVE: To study which factors affect perinatal outcomes in intracytoplasmic sperm injection (ICSI) cycles. METHODS: Data was obtained from 402 live births born to 307 patients undergoing ICSI cycles in a private university-affiliated IVF center between Jan/2014 and Dec/2015. The influences of the cycles' characteristics on the number of gestational weeks to livebirth (GW), baby birth weight (BW), and baby birth length (BL) were evaluated by linear regression models, adjusted for maternal age and body mass index, number of transferred embryos, number of gestational sacs, and number of born infants. In a subsequent analysis, GW, BW and baby sex were utilized for cycle classification into the groups Appropriate for gestational age (AGA n=256) and Small for gestational age (SGA n=146), which were compared by general linear models adjusted for the same confounder variables. RESULTS: The number of follicles (ß=-0.069 p=0.018) and retrieved oocytes (ß=-0.087 p=0.049) were negatively correlated with BL. The endometrial thickness was positively correlated with GW (ß=0.198 p=0.003) and BW (ß=28.351 p=0.044). When each baby was classified into AGA and SGA groups, it was observed that SGA babies were derived from cycles with higher estradiol levels at hCG day (SGA: 3897.01±550.35 vs. AGA: 2324.78±101.86 p=0.006) and higher number of retrieved oocytes (SGA: 16.70±1.78 vs. AGA: 12.92±0.42 p=0.042). The endometrial thickness was significantly lower in the SGA group (SGA: 10.2±0.23 vs. AGA: 11.68±0.17 vs. p=0.029). CONCLUSION: Higher ovarian response to stimulation and suboptimal endometrial development are associated with adverse perinatal outcomes in ICSI cycles.

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