Serum miR-181d-5p levels in response to controlled ovarian stimulation: predictive value and biological function.

The response to controlled ovarian stimulation (COS) for in vitro fertilization (IVF) varies dramatically from one patient to another, affecting success rates. A previous large-scale study identified increased serum miR-181d-5p levels in patients with high response to COS prior to stimulation. We aim to evaluate whether the expression of miR-181d-5p differs according to the ovarian response to COS in women undergoing intracytoplasmic sperm injection (ICSI) cycles. Samples collected prior to COS for ICSI were split into three groups depending on the ovarian response to COS: poor response (PR), <4 oocytes retrieved (n=25); normal response (NR), ≥8 and ≤12 oocytes retrieved (n=21); and high response (HR), >25 oocytes retrieved (n=20). miR-181d-5p serum levels were compared among experimental groups. miR-181d-5p levels were increased in the HR group when compared to the PR (p=0.0001) and NR groups (p=0.0079). miR-181d-5p levels correlated with the number of aspirated follicles (p<0.0001), retrieved oocytes (p<0.0001), and mature oocytes (p=0.0002). Increased miR-181d-5p levels independently predict a high response (p=0.006), with Positive and Negative Predictive Values of 66.7% and 69.4%, respectively. miR-181d-5p was also detected in the ovarian tissue in a mouse model. Moreover, computational analysis of miR-181d-5p predicted targets and promoter region suggested that this miRNA might be involved in the regulation of key signaling pathways and biological processes for female reproductive biology. In conclusion, miR-181d-5p is a promising circulating predictor of high stimulation and potential mediator of the hypothalamus-pituitary-gonad axis, providing opportunities for the individualization of COS protocols.

SARS-CoV-2 pandemic and repercussions for male infertility patients: A proposal for the individualized provision of andrological services.

The prolonged lockdown of health facilities providing non-urgent gamete cryopreservation-as currently recommended by many reproductive medicine entities and regulatory authorities due to the SARS-CoV-2 pandemic will be detrimental for subgroups of male infertility patients. We believe the existing recommendations should be promptly modified and propose that the same permissive approach for sperm banking granted for men with cancer is expanded to other groups of vulnerable patients. These groups include infertility patients (eg, azoospermic and cryptozoospermic) undergoing medical or surgical treatment to improve sperm quantity and quality, as well as males of reproductive age affected by inflammatory and systemic auto-immune diseases who are about to start treatment with gonadotoxic drugs or who are under remission. In both scenarios, the "fertility window" may be transitory; postponing diagnostic semen analysis and sperm banking in these men could compromise the prospects of biological parenthood. Moreover, we provide recommendations on how to continue the provision of andrological services in a considered manner and a safe environment. Our opinion is timely and relevant given the fact that fertility services are currently rated as of low priority in most countries.

Serum metabolites as predictive molecular markers of ovarian response to controlled stimulation: a pilot study.

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.

Ovarian response to stimulation and suboptimal endometrial development are associated with adverse perinatal outcomes in intracytoplasmic sperm injection cycles.

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.

Preimplantation genetic testing for monogenic diseases: a Brazilian IVF centre experience.

OBJECTIVE: To describe the cases of preimplantation genetic testing for monogenic diseases (PGT-M) in fertile couples who had undergone intracytoplasmic sperm injection (ICSI) cycles in a Brazilian in vitro fertilisation (IVF) centre and determine whether these cases were different from those reported from the European Society of Human Reproduction and Embryology (ESHRE). METHODS: This retrospective collection included data obtained from ICSI-PGT-M cycles between 2011 and 2016. The disease indication, number of biopsied embryos, biopsy stage, diagnosed and affected embryos, and cycles with embryo to transfer as well as implantation, pregnancy and miscarriage rates were analysed and compared to cycles without genetic diagnosis (PGT) and with ESHRE PGD Consortium collection XIV-XV. RESULTS: From 5,070 cycles performed, 72 had indications for PGT-M. The most common time for biopsy was cleavage-stage; 93% of the embryos had a diagnostic result, 59.4% of which were genetically transferable, resulting in 68% of the cycles with transferred embryos, a 22.1% implantation rate, and a 28.6% pregnancy rate. No differences in clinical outcomes of cycles with PGT-M or without PGT were observed. The day of biopsy and diagnostic success as well as implantation, pregnancy and miscarriage rates were similar to ESHRE collection. CONCLUSIONS: Although the proportion of cases with PGT-M was low, its efficacy was similar to what was reported in the European collection and represents a viable alternative for families at risk of transmitting a genetic disorder to their offspring. The main difference between our and ESHRE collection were the disease indications, which reflected the admixed, multi-ethnic Brazilian population.

Role of religion, spirituality, and faith in assisted reproduction.

Purpose: The purpose of this study is to evaluate the impact of the patient's faith, religion, and spirituality on the outcomes of intracytoplasmic sperm injection (ICSI) cycles. Materials and methods: Eight hundred and seventy-seven patients received a questionnaire containing information on faith, religiosity, and spirituality and the results of the questionnaires were correlated with ICSI outcomes. Patients stated to be Catholic (n = 476), spiritists (n = 93), Evangelical (n = 118), and other religion (n = 32), and 78 did not identify with any religious group. Results: A significant increase in fertilization, high-quality embryos, and pregnancy rate was found among Spiritists and Evangelicals. Patients who included the infertility diagnosis and treatment in their prayers showed an increased pregnancy rate, and those who reported their faith to be affected by the infertility diagnosis presented a decreased high-quality embryos rate. The high-quality embryos rate was increased among patients who answered that their faith contributed to their decision to undergo infertility treatment. The cycle's cancelation was negatively correlated with the frequency of religious meetings, and the frequency of prayers was positively correlated with the response to ovarian stimulation. Finally, belief in treatment success positively influenced the embryo quality. Conclusion: The findings suggest that spirituality plays a role in adjusting the psychological aspects of an infertile patient.

Association between parental anthropometric measures and the outcomes of intracytoplasmic sperm injection cycles.

PURPOSE: To study the association between body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), and response to controlled ovarian stimulation, semen quality, and intracytoplasmic sperm injection (ICSI) outcomes. METHODS: This prospective observational study included data from 402 couples undergoing ICSI between January/2010-September/2016. Participants had their weight, height, waist, and hip measured before ICSI treatment. RESULTS: Gonadotropin dose was positively associated with maternal WHR. Maternal WC and WHR negatively influenced the estradiol level, number of follicles, oocytes, and mature oocytes. Maternal BMI negatively influenced oocyte yield. Semen volume was negatively influenced by male BMI. Sperm concentration was negatively associated with WHR and WHtR. Progressive sperm motility was negatively influenced by all anthropometric measures (AMs). The TMSC was negatively affected by all AM but WC. Significant differences were observed in all ICSI outcomes except pregnancy and miscarriage rates, favoring women with AM below the cut off values compared to women above the cut off. It was observed that men with AM below the cut off values showed significantly higher rates of fertilization, embryo and blastocyst development, implantation, and pregnancy than men above the cut off. When combined maternal and paternal AM were analyzed, significant differences were observed in fertilization, embryo and blastocyst development and implantation rates, favoring couples with normal BMI, WC, and WHR. CONCLUSIONS: Lower AMs have a protective effect on fertility. Awareness and counseling on how to minimize its impact in both partners could improve ICSI outcomes.

Lipidomic profile as a noninvasive tool to predict endometrial receptivity.

For the present study we asked whether the endometrial fluid lipidomic may be a useful approach to predict endometrial receptivity in freeze-all cycles. For this case-control study, endometrial fluid samples were collected from 41 patients undergoing freeze-all cycles. Samples were split depending on the pregnancy outcome: positive group (n = 24) and negative group (n = 17). Data were acquired by the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were applied. A list of potential biomarker ion ratios was obtained and the values were used to build a receiver operating characteristic (ROC) curve to predict pregnancy success. The lipid categories were attributed by LIPID MAPS database. Ion ratios were established according to their correlations and used for the analysis. The PCA showed a tendency of separation between the studied groups, whereas the PLS-DA was able to clearly distinguish them. Fifteen ratios (13 hyper-represented in the negative and two hyper-represented in the positive group) were selected according to their importance for model prediction. These ratios were used to build the ROC curve, which presented an area under curve of 84.0% (95%CI: 69.2-97.4%; p = 0.009). These findings suggest that lipidomic profiling of endometrial fluid may be a valuable tool for identifying the time interval comprising the window of implantation.

Paternal lifestyle factors in relation to semen quality and in vitro reproductive outcomes.

This prospective-cohort study aimed at investigating the influence of paternal lifestyle factors on semen parameters and intracytoplasmic sperm injection (ICSI) outcomes. The influence of paternal lifestyle factors on seminal quality and ICSI outcomes was investigated in male patients undergoing conventional semen analysis. Cigarette smoking negatively influenced semen volume (B: -0.417, slope: 1.570, p = 0.047), sperm count/ml (B: -7.363, slope: 52.298, p = 0.014), total sperm count (B: -4.43, slope: 178.165, p = 0.023), total motile sperm count (B: -1.38, slope: 100.276, p = 0.045) and SDF (B: 0.014, slope: 9.767, p = 0.033). Alcohol consumption negatively influenced sperm count/ml (B: -12.527, slope: 42.255, p = 0.040) and sperm DNA fragmentation (B: 5.833, slope: 9.680, p = 0.002). There were no significant influences of other paternal lifestyle factors. Cigarette smoking negatively influenced the fertilisation rate (B: -1.349, slope: 21.950, p = 0.039) and the blastocyst formation rate (B: -14.244, slope: 28.851, p = 0.025). Alcohol consumption negatively influenced fertilisation rate (B: -3.617, slope: 20.138, p = 0.041) and blastocyst formation rate (B: -34.801, slope: 30.044, p = 0.042). Cigarette smoking and alcohol consumption appear to reduce semen quality, fertilisation and blastocyst formation rates; thus, it would be wise to recommend that male partners reconsider their lifestyle during in vitro reproduction treatment.

Blastomere nucleation: Predictive factors and influence of blastomere with no apparent nuclei on blastocyst development and implantation.

OBJECTIVE: To investigate whether embryos presenting blastomere(s) with no apparent nucleus (BNAN) on days 2 and 3 are more likely to fail to develop into blastocysts, hatch and implant. METHODS: A total of 5705 zygotes obtained from 743 intracytoplasmic sperm injection (ICSI) cycles were analyzed. The presence and incidence of BNAN on days 2 and 3 of embryo development were recorded and then associated with ICSI outcomes. RESULTS: The occurrence of BNAN on day 2 of embryo development was determinant to the decreased odds of blastocyst formation (OR: 0.57, CI: 0.50-0.65), quality (OR: 0.56, CI: 0.43-0.73) and hatching status (OR: 0.66, CI: 0.50-0.87). The presence of BNAN on day 3 of embryo development was determinant to the decreased odds of blastocyst formation (OR: 0.67, CI: 0.58-0.78) and hatching status (OR: 0.61, CI: 0.45-0.83). The occurrence of BNAN on day 2 of embryo development was determinant to the decreased odds of blastocyst implantation (OR: 0.50, CI: 0.27-0.94). CONCLUSION: The presence of BNAN on day 2 or day 3 reduces development to blastocyst stage, hatching and implantation. Careful nuclear observation, taking into account the absence of blastomere nucleus, should be part of the strategies used for embryo selection.

Is there an association between artificial sweetener consumption and assisted reproduction outcomes?

Previous studies have suggested an association between high intake of sweetened beverages and a number of adverse health outcomes. In this cross-sectional study, we investigated the association between daily consumption of sweetened soft drinks or coffee and the outcome of intracytoplasmic sperm injection (ICSI) treatment. Patients (n = 524) were interviewed by a nutritionist before ICSI treatment, using a food frequency questionnaire. Regression analysis showed that consumption of ≥3 servings of regular soft drinks or any amount of diet soft drinks was associated with oocyte dysmorphism, diminished embryo quality on days 2 and 3 of culture, and a mild effect on blastocyst formation, implantation and pregnancy rate. Consumption of artificially sweetened coffee was negatively associated with embryo quality on days 2 and 3. However, consumption of coffee or soft drinks was not associated with the odds of live birth. Even so, patients should be advised about the potential negative effects of sugar and artificial sweeteners before attempting infertility treatment. This study is limited by the use of a non-validated food frequency questionnaire, lack of information on quantity of sweeteners consumed, and lack of data on glucose levels in blood serum or follicular fluid. Further investigation is warranted.

FSH dose to stimulate different patient' ages: when less is more.

OBJECTIVE: To determine the effect of FSH doses on intracytoplasmic sperm injection (ICSI) outcomes according to the age of the patient. METHODS: Patients undergoing controlled ovarian stimulation (COS) for ICSI cycles in a university-affiliated in vitro fertilization center were split into age groups: ≤35 y.o. (n=1523); >35 and ≤38 y.o. (n=652); >38 and ≤40 y.o. (n=332); and >40 y.o. (n=370). The effect of FSH dose on COS, laboratorial and clinical outomes was determined by linear regression models. RESULTS: The FSH dose didn't affect the ovarian response in terms of total number of follicles, retrieved oocytes and mature oocytes within the age groups, but we found that the lower the age, the lower the FSH dose needed per oocyte retrieved. In the group of patients ≤35 y.o., we also found a positive effect of the FSH dose on oocyte yield. Despite that, for patients ≤38 y.o. there was a negative effect of the FSH dose on embryo quality and blastocyst formation rate, and an increase in the cycle's cancelation rate. In patients ≥39 y.o., there were no effects of the FSH doses on the analysed variables. CONCLUSIONS: Ovarian stimulation with high doses of FSH is not recommended in younger women (≤38 y.o.), once we found a decrease in embryo quality and an increase in cycle's cancelation rate. Mild ovarian stimulation protocols may be more appropriate; however, it may not be applicable for women in advanced age, since a higher FSH dose is needed for oocyte retrieval in these patients.

Overcoming male factor infertility with intracytoplasmic sperm injection.

OBJECTIVE: To evaluate the effect of male factor infertility on intracytoplasmic sperm injection (ICSI) outcomes compared with a control group presenting isolated tubal factor. METHOD: This retrospective study included 743 couples undergoing ICSI as a result of isolated male factor and a control group consisting of 179 couples undergoing ICSI as a result of isolated tubal factor, performed in a private university- -affiliated in vitro fertilization center, between January/2010 and December/2016. Patients were divided into two groups according to maternal age: women ≤35 years old and >35 years old. The effects of infertility causes on laboratorial and clinical ICSI outcomes were evaluated using Student's t-test and (2 test. RESULTS: No differences in controlled ovarian stimulation outcomes were observed between male factor cycles and tubal factor cycles in the two age groups. Implantation (male factor 35.5% vs. tubal factor 32.0%, p=0.340), pregnancy (male factor 46.9% vs. tubal factor 40.9%, p=0.184) and miscarriage (male factor 10.3% vs. tubal factor 10.6%, p=0.572) rates were similar between the infertility groups, irrespective of female age. Considering maternal age, the cancelation rate was higher in older women (>35 years old) undergoing ICSI as a result of male factor infertility (17.4% vs. 8.9%, p=0.013). CONCLUSION: Our results showed that there is no difference in the outcomes of pregnancy between couples with male or tubal factor infertility, which indicates that ICSI surpasses the worse specific outcomes associated with male factor.

The predictive value of serum concentrations of anti-Müllerian hormone for oocyte quality, fertilization, and implantation.

OBJECTIVE: This study aimed to identify a possible correlation between serum levels of anti-Müllerian hormone (AMH) and oocyte quality, embryo developmental competence, and implantation potential. METHODS: 4488 oocytes obtained from 408 patients undergoing ICSI cycles were evaluated. Oocyte dimorphisms, embryo quality on days two and three, blastocyst formation competence, fertilization rates, implantation rates, and pregnancy rates were correlated with serum levels of AMH using Pearson's correlation coefficient and regression analysis. RESULTS: A positive correlation was observed between serum levels of AMH and number of retrieved oocytes (CC: 0.600, p<0.001), fertilization rate (CC:0.595, p=0.048), and number of obtained embryos (CC:0.495, p<0.001). AMH did not affect the quality of cleavage stage embryos or the chance of blastocyst formation. However, AMH levels affected oocyte quality (OR:0.75, CI 0.44-0.96, p<0.001), and implantation (CC:0,116, p=0.031) and pregnancy (OR:1.22, CI:1.03-1.53, p<0.001) rates. CONCLUSION: Serum levels of AMH are a useful predictor of ovarian response to COS, oocyte quality, and fertilization. However, AMH levels may also compromise clinical outcomes; lower AMH levels did not impair embryo development.

Overcoming male factor infertility with intracytoplasmic sperm injection / Superando o fator masculino de infertilidade com injeção intracitoplasmática de espermatozoides

Summary Objective: To evaluate the effect of male factor infertility on intracytoplasmic sperm injection (ICSI) outcomes compared with a control group presenting isolated tubal factor. Method: This retrospective study included 743 couples undergoing ICSI as a result of isolated male factor and a control group consisting of 179 couples undergoing ICSI as a result of isolated tubal factor, performed in a private university- -affiliated in vitro fertilization center, between January/2010 and December/2016. Patients were divided into two groups according to maternal age: women ≤35 years old and >35 years old. The effects of infertility causes on laboratorial and clinical ICSI outcomes were evaluated using Student's t-test and (2 test. Results: No differences in controlled ovarian stimulation outcomes were observed between male factor cycles and tubal factor cycles in the two age groups. Implantation (male factor 35.5% vs. tubal factor 32.0%, p=0.340), pregnancy (male factor 46.9% vs. tubal factor 40.9%, p=0.184) and miscarriage (male factor 10.3% vs. tubal factor 10.6%, p=0.572) rates were similar between the infertility groups, irrespective of female age. Considering maternal age, the cancelation rate was higher in older women (>35 years old) undergoing ICSI as a result of male factor infertility (17.4% vs. 8.9%, p=0.013). Conclusion: Our results showed that there is no difference in the outcomes of pregnancy between couples with male or tubal factor infertility, which indicates that ICSI surpasses the worse specific outcomes associated with male factor.

Resumo Objetivo: Avaliar o efeito do fator masculino de infertilidade em resultados de injeção intracitoplasmática de espermatozoides (ICSI) em comparação com um grupo controle que apresenta o fator tubário isolado. Método: Este estudo retrospectivo incluiu 743 casais submetidos a ICSI por fator masculino e 179 casais por fator tubário, realizada em um centro privado de fertilização in vitro associado à universidade, entre janeiro de 2010 e dezembro de 2016. Os pacientes foram divididos em dois grupos de acordo com a idade materna: mulheres ≤ 35 e > 35 anos de idade. Os efeitos das causas de infertilidade nos resultados laboratoriais e clínicos da ICSI foram avaliados pelos testes T de Student e Qui-quadrado. Resultados: Não foram observadas diferenças nos parâmetros de estimulação ovariana entre os ciclos com fatores masculinos e com fatores tubários. A taxa de implantação (fator masculino 35,5% vs. fator tubário 32,0%, p=0,340), de gravidez (fator masculino 46,9% vs. fator tubário 40,9%, p=0,184) e de aborto (fator masculino 10,3% vs. fator tubário 10,6%, p=0.572) foram semelhantes entre os grupos de infertilidade, independentemente da idade feminina. Considerando a idade materna, a taxa de cancelamento foi maior em mulheres > 35 anos cuja causa de infertilidade era o fator masculino (17,4% vs. 8,9%, p=0,013). Conclusão: Não há diferenças nos resultados de gravidez entre casais com infertilidade dos fatores masculino ou tubário isolados, o que indica que ICSI supera os piores resultados associados ao fator masculino.

Oocytes with smooth endoplasmic reticulum clusters originate blastocysts with impaired implantation potential.

OBJECTIVE: To study whether embryos derived from oocytes presenting a smooth endoplasmic reticulum cluster (SERC) are less likely to develop into blastocysts and implant. DESIGN: Transversal study. SETTING: Private university-affiliated in vitro fertilization (IVF) center. PATIENT(S): Total of 7,609 oocytes obtained from 743 intracytoplasmic sperm injection (ICSI) cycles. INTERVENTION(S): Oocytes split between the SERC-positive cycles (with at least one SERC-positive oocyte) and the SERC-negative cycles (only oocytes free of SERC). MAIN OUTCOME MEASURE(S): Embryo implantation. RESULT(S): A statistically significantly higher mean number of follicles (24.0 ± 10.5 vs. 19.6 ± 10.5), retrieved oocytes (17.8 ± 8.3 vs. 14.3 ± 8.0), and mature oocytes (13.5 ± 6.2 vs. 10.6 ± 5.9) were observed in the SERC-positive cycles as compared with SERC-negative cycles. The implantation rate was statistically significantly lower in SERC-positive cycles as compared with SERC-negative cycles (14.8% vs. 25.6%; odds ratio 0.61; 95% confidence interval, 0.44-0.86). When only cycles with in which none (0) or all the blastocysts transferred had implanted (100%) were analyzed, the mean implantation rate per transferred blastocyst in the SERC-negative group was 20.5%; no blastocysts derived from SERC-positive oocytes implanted. CONCLUSION(S): The occurrence of SERC impairs embryo implantation. Careful oocyte observation that takes into account the presence of SERC should be part of embryo selection strategy before transfer.

Protein expression in human cumulus cells as an indicator of blastocyst formation and pregnancy success.

PURPOSE: The goal for the present study was to implement a technique for protein extraction and identification in human cumulus cells (CCs). METHODS: Forty samples of CCs were collected after ovum pick-up from patients undergoing intracytoplasmic sperm injection (ICSI). Samples were split into the blastocyst group (n = 10), including patients in which all embryos converted into blastocysts, and the non-blastocyst group (n = 10), including patients in which none of the embryos reached the blastocyst stage or the positive-pregnancy (n = 10) and negative-pregnancy group (n = 10). Proteins were extracted and injected into a liquid chromatography system coupled to a mass spectrometer. The spectra were processed and used to search a database. RESULTS: There were 87 different proteins in samples from the blastocyst and non-blastocyst groups, in which 30 were exclusively expressed in the blastocyst group and 17 in the non-blastocyst group. Among the 72 proteins detected in the pregnancy groups, 19 were exclusively expressed in the positive, and 16 were exclusively expressed in the negative-pregnancy group. CONCLUSIONS: CC proteomics may be useful for predicting pregnancy success and the identification of patients that should be included in extended embryo culture programs.

Freeze-all, oocyte vitrification, or fresh embryo transfer? Lessons from an egg-sharing donation program.

OBJECTIVE: To compare the outcomes of ETs using cryopreserved embryos, cryopreserved oocytes, or fresh embryos. DESIGN: Observational, cohort study. SETTING: Private university-affiliated fertility center. PATIENT(S): This study included 8,210 mature oocytes obtained from 425 oocyte donors. Of those, 5,440 were used for the donors' own cycles (Fresh Oocyte Cycles Group), and 2,770 were cryobanked for 425 recipients (Banked Donor Egg Group). All of the oocytes were sperm injected, resulting in 4,585 embryos from the donors' own cycles and 2,128 embryos from the recipients' cycles. For the donor cycles, embryos were either cryopreserved and transferred during a subsequent cycle (Thaw Cycles Group, 3,209 embryos), or they were transferred during a fresh cycle (Fresh Cycles Group, 1,307 embryos). For the recipient cycles, embryos derived from vitrified oocytes were transferred (Vitrified Oocytes Group, n = 425 cycles, 2,128 embryos). INTERVENTION(S): Oocyte/embryo vitrification and intracytoplasmic sperm injection. MAIN OUTCOME MEASURE(S): Embryo quality, pregnancy, and implantation rates. RESULT(S): Decreased embryo quality and lower rates of blastocyst formation were observed among embryos derived from vitrified oocytes. The highest pregnancy and implantation rates were noted for the Thaw Cycles Group, followed by the Banked Donor Egg Group; the Fresh Cycles Group had the lowest rates. CONCLUSION(S): Oocyte vitrification followed by intracytoplasmic sperm injection leads to lower embryo developmental competence compared with when fresh insemination methods are used. However, pregnancy and implantation rates are higher when embryos are transferred into a "more receptive" endometrium, free of the adverse effects of gonadotropin. Moreover, the freeze-all method leads to exceptional clinical outcomes.

Strategies for the management of OHSS: Results from freezing-all cycles.

OBJECTIVE: To compare the use of GnRH agonist (GnRHa) or hCG trigger in potential OHSS patients undergoing freeze-all programs. We also compared the clinical outcomes when fresh versus freeze-thawed embryo transfers were performed in cycles with a high number of retrieved oocytes. METHODS: The study included potential OHSS patients who received GnRHa (n=74) or hCG (n=49) trigger. The protocols were compared with respect to the clinical outcomes. We also compared the clinical outcomes of cycles in which hCG trigger was used and more than 20 MII oocytes were retrieved when: fresh embryo transfer protocol (n=153) or freeze-all protocol (n=123) were performed. RESULTS: A decreased serum estradiol level, a decreased number of retrieved oocytes, an increased MII retrieved rate, and decreased fertilization rate was observed in the hCG when compared with the GnRHa group. No significant differences were noted concerning clinical outcomes. When fresh cycles were compared with frozen-thawed cycles, the estradiol serum level and the number of cryopreserved embryos were higher in the frozen-thawed cycles. The clinical pregnancy rate was higher among freeze-all cycles, as well as the implantation and cumulative pregnancy rates, when compared with fresh embryo transfer cycles. CONCLUSION: The use of GnRHa trigger may be a good alternative to prevent the OHSS in patients presenting an extreme ovarian response to COS, leading to similar clinical outcomes, when compared with the traditional hCG trigger. Moreover, our findings demonstrated that the strategy of freezing-all embryos not only decreases the risk of OHSS but also leads to a better pregnancy rate.