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Cavagna M.,Fertility Assisted Fertilization Center | Cavagna M.,Sapientiae Institute Educational and Research Center in Assisted Reproduction | Cavagna M.,Perola Byington Hospital | Maldonado L.G.L.,Fertility Assisted Fertilization Center | And 7 more authors.
Fertility and Sterility | Year: 2010

Objective: To compare the outcomes of protocols for ovarian stimulation with recombinant hCG microdose, with GnRH agonists and antagonists for pituitary suppression. Design: Prospective nonrandomized clinical trial. Setting: A private assisted reproduction center. Patient(s): We studied 182 patients undergoing intracytoplasmic sperm injection (ICSI) cycles, allocated into two groups: GnRH agonist group, in which patients received a GnRH agonist (n = 73), and a GnRH antagonist group, in which patients were administered a GnRH antagonist for pituitary suppression (n = 109). Intervention(s): Pituitary suppression with GnRH agonist or GnRH antagonist. Ovarian stimulation carried out with recombinant FSH and supplemented with recombinant hCG microdose. Main Outcome Measure(s): Total dose of recombinant FSH and recombinant hCG administered; E2 concentrations and endometrial width on the day of hCG trigger; number of follicles aspirated, oocytes and mature oocytes retrieved; fertilization, pregnancy (PR), implantation, and miscarriage rates. Result(s): The total dose of recombinant FSH and recombinant hCG administered were similar between groups, as were the E2 concentrations and endometrial width. The number of follicles aspirated, oocytes, and metaphase II oocytes collected were also comparable. There were no statistically significant differences in fertilization, PR, implantation, and miscarriage rates in the GnRH agonist and GnRH antagonist groups. Conclusion(s): When using recombinant hCG microdose supplementation for controlled ovarian stimulation (COS), there are no differences in laboratory or clinical outcomes with the use of either GnRH antagonist or agonist for pituitary suppression. © 2010 American Society for Reproductive Medicine.


Maldonado L.G.L.,São Paulo State University | Franco Jr. J.G.,São Paulo State University | Franco Jr. J.G.,Prof Franco Jresearch Center For Human Reproduction | Setti A.S.,Sapientiae Institute Educational and Research Center in Assisted Reproduction | And 5 more authors.
Fertility and Sterility | Year: 2013

Objective: To compare cost-effectiveness between pituitary down-regulation with a GnRH agonist (GnRHa) short regimen on alternate days and GnRH antagonist (GnRHant) multidose protocol on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcome. Design: Prospective, randomized. Setting: A private center. Patient(s): Patients were randomized into GnRHa (n = 48) and GnRHant (n = 48) groups. Intervention(s): GnRHa stimulation protocol: administration of triptorelin on alternate days starting on the first day of the cycle, recombinant FSH (rFSH), and recombinant hCG (rhCG) microdose. GnRHant protocol: administration of a daily dose of rFSH, cetrorelix, and rhCG microdose. Main Outcome Measure(s): ICSI outcomes and treatment costs. Result(s): A significantly lower number of patients underwent embryo transfer in the GnRHa group. Clinical pregnancy rate was significantly lower and miscarriage rate was significantly higher in the GnRHa group. It was observed a significant lower cost per cycle in the GnRHa group compared with the GnRHant group ($5,327.80 ± 387.30 vs. $5,900.40 ± 472.50). However, mean cost per pregnancy in the GnRHa was higher than in the GnRHant group ($19,671.80 ± 1,430.00 vs. $11,328.70 ± 907.20). Conclusion(s): Although the short controlled ovarian stimulation protocol with GnRHa on alternate days, rFSH, and rhCG microdose may lower the cost of an individual IVF cycle, it requires more cycles to achieve pregnancy. Clinical Trial Registration Number: NCT01468441. © 2013 by American Society for Reproductive Medicine.


Cortezzi S.S.,Sapientiae Institute Educational and Research Center in Assisted Reproduction | Garcia J.S.,Federal University of Alfenas | Ferreira C.R.,University of Campinas | Braga D.P.A.F.,Sapientiae Institute Educational and Research Center in Assisted Reproduction | And 7 more authors.
Analytical and Bioanalytical Chemistry | Year: 2011

A bottom-up label-free mass spectrometric proteomic strategy was used to analyse the protein profiles of the human embryonic secretome. Culture media samples used for embryonic culture of patients undergoing intracytoplasmic sperm injection cycles were selected as a test case for this exploratory proof-of-principle study. The media were stored after embryo transfer and then pooled into positive (n∈=∈8) and negative (n∈=∈8) implantation groups. The absolute quantitative bottom-up technique employed a multidimensional protein identification technology based on separation by nano-ultra-high pressure chromatography and identification via tandem nano-electrospray ionization mass spectrometry with data-independent scanning in a hydrid QqTOF mass spectrometer. By applying quantitative bottom-up proteomics, unique proteins were found exclusively in both the positive- and negative-implantation groups, which suggest that competent embryos express and secrete unique biomarker proteins into the surrounding culture medium. The selective monitoring of these possible secretome biomarkers could make viable procedures using single-embryo transfer. [Figure not available: see fulltext.] © 2011 Springer-Verlag.


Setti A.S.,Sapientiae Institute Educational and Research Center in Assisted Reproduction | Cortezzi S.S.,Sapientiae Institute Educational and Research Center in Assisted Reproduction | Figueira R.D.C.S.,Fertility Assisted Fertilization Center | Martinhago C.D.,RDO Medical Diagnosis | And 5 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2012

Purpose To evaluate if several genetic loci that are associ- ated with variation in normal menopause age and early menopause can account for a poor response to controlled ovarian stimulation. Methods A total of 71 patients age ≥35 years old who were undergoing intracytoplasmic sperm injection were genotyped for four genetic variants that are associated with normal variation in menopausal age and early menopause. The patients were divided into two groups based upon treatment response: a poor responder group (PR group, n = 21) and a normal responder group (NR group, n =n 50). The genetic variants rs244715, rs9379896,rs4806660 and rs16991615 were analyzed. Results There was no significant difference in the incidence of the genetic variants between the NR and PR group. The risk allele for the chromosome 19 variant (rs4806660) demonstrated a protective effect for a poor ovarian response. The presence of a risk allele was associated with an increased response to COS, which resulted in an elevated number of follicles (Coef: 2.54, P = 0.041) and retrieved oocytes (Coef: 1.41, P = 0.041). Conclusions The genetic variants rs244715, rs9379896, rs4806660 and rs16991615 are not risk factors for poor ovarian response in Brazilian women. In contrast, rs4806660 is associated with higher number of follicles and retrieved oocytes. rs4806660 may be associated with an increased response to gonadotrophin stimulation in this population. © 2012 The Author(s).


Braga D.P.D.A.F.,Fertility Assisted Fertilization Center | Braga D.P.D.A.F.,Sapientiae Institute Educational and Research Center in Assisted Reproduction | Halpern G.,Fertility Assisted Fertilization Center | Figueira R.D.C.S.,Fertility Assisted Fertilization Center | And 4 more authors.
Fertility and Sterility | Year: 2012

Objective: To investigate the influence of the male partner's lifestyle, including eating and social habits, on semen quality and intracytoplasmic sperm injection (ICSI) success. Design: Observational study. Setting: Private fertility clinic. Patient(s): Two hundred fifty male patients undergoing ICSI cycles. Intervention(s): We recorded dietary and social habits using a food frequency questionnaire adapted to meet specific study objectives. Evaluation of semen parameters and ICSI outcomes were performed. Main Outcome Measure(s): Frequency of intake of food items and social habits were registered on a scale with five categories ranging from no consumption to repeated daily consumption. Result(s): The sperm concentration was negatively influenced by body mass index (BMI) and alcohol consumption and was positively influenced by cereal consumption and the number of meals per day. The sperm motility was also negatively influenced by BMI, alcohol consumption, and smoking habit, whereas it was positively influenced by the consumption of fruits and cereals. The consumption of alcohol had a negative influence on the fertilization rate. The consumption of red meat as well as being on a weight loss diet had a negative impact on the implantation rate. In addition, the consumption of red meat and being on a weight loss diet had an effect on the pregnancy chance. Conclusion(s): Couples seeking assisted reproduction treatments must be advised about the drastic effect of both the male and female lifestyle on treatment success.


Figueira R.D.C.S.,Fertility Assisted Fertilization Center | Braga D.P.A.F.,Fertility Assisted Fertilization Center | Braga D.P.A.F.,Sapientiae Institute Educational and Research Center in Assisted Reproduction | Setti A.S.,Sapientiae Institute Educational and Research Center in Assisted Reproduction | And 3 more authors.
Fertility and Sterility | Year: 2011

Objective: To examine the effect of sperm morphology on embryo development at the chromosomal level. Design: Prospective study. Setting: Assisted fertilization center. Patient(s): Couples who underwent IVF-PGS cycle, as a result of advanced maternal age, were randomly allocated into two groups: intracytoplasmic sperm injection (ICSI; n = 60) or intracytoplasmic morphologically selected sperm injection (IMSI; n = 60). Intervention(s): IVF in conjunction with preimplantation genetic screening (PGS). Main Outcome Measure(s): Sperm nuclear morphology at high-magnification ICSI and incidence of aneuploidy in derived embryo. Result(s): There was a significantly increased incidence for sex chromosome aneuploidy in ICSI embryos when compared with IMSI embryos (23.5% vs. 15.0%, respectively). High-magnification sperm selection was associated with a significantly lower risk of sex chromosome abnormalities (odds ratio [OR], 0.57; confidence interval [CI], 0.37-0.90). The incidence of chaotic embryos was also significantly higher with the ICSI procedure (27.5% vs. 18.8%), while the IMSI procedure was associated with a significantly lower risk of chaotic embryos (OR, 0.64; CI, 0.43-0.96). Moreover, the cycle cancellation rate was significantly higher in ICSI cycles (11.8% vs. 2.5%). High-magnification sperm selection was a significant predictor of the likelihood of cycle cancellation (OR, 0.26; CI, 0.11-0.62). Conclusion(s): Spermatozoa free of nuclear morphological malformations were found to be significantly associated with the lower incidence of aneuploidy in derived embryos, resulting in lower rates of cycle cancellation. ©2011 by American Society for Reproductive Medicine.


PubMed | Sapientiae Institute Educational and Research Center in Assisted Reproduction
Type: Journal Article | Journal: Journal of assisted reproduction and genetics | Year: 2012

To evaluate the relationship between oocyte dysmorphisms and IMSI outcomesData of IMSI cycles performed in 332 patients were included in this study. Patients were included only if presented more than four and less than 30 oocytes upon oocyte retrieval. Patients who underwent IMSI were matched, concerning female age and sperm parameters, with patients who underwent ICSI in the same period (n=332). The two groups (ICSI and IMSI) were compared with regard to treatment outcomes. The influence of IMSI on fertilization and embryo quality on D3 and D5, when oocyte dysmorphisms were present was analyzed.A total of 6444 oocytes were morphologically evaluated and injected. Regardless of the oocyte quality, IMSI performance was a determinant of the increased odds of development to high quality embryo on D3 (OR: 1.98; CI: 1.54-2.56) and D5 (OR: 3.27; CI: 1.61-6.66).The selection of a morphologically normal spermatozoon under high-magnification is associated with increased embryo quality, regardless of the oocyte morphology. The injection of a spermatozoon, selected under high-magnification, into a morphologically normal oocyte leads to the highest probability of developing high quality embryos.


PubMed | Sapientiae Institute Educational and Research Center in Assisted Reproduction
Type: Journal Article | Journal: Reproductive biomedicine online | Year: 2012

The aim of this prospective randomized study was to determine if the use of intracytoplasmic morphologically selected sperm injection (IMSI) is associated with gender incidence. Couples who underwent IVF-preimplantation genetic screening (PGS) cycles, as a result of advanced maternal age, were randomly allocated into two groups: intracytoplasmic sperm injection (ICSI; n=80) or intracytoplasmic morphologically selected sperm injection (IMSI; n=80). The incidences of genders were compared between ICSI- and IMSI-derived embryos. Considering all the biopsied embryos were characterized as normal for sex chromosome, the results showed that IMSI results in a significantly higher incidence of female embryos as compared with ICSI (65.1% versus 54.0%, respectively, P=0.0277). After analysing only euploid embryos for the eight selected chromosomes, a significantly higher incidence of XX embryos derived from IMSI was also observed compared with ICSI cycles (66.9% versus 52.5%, respectively, P=0.0322). This result was confirmed by logistic regression, which demonstrated a nearly 2-fold increase in euploid XX embryos derived from spermatozoa selected by high magnification (OR 1.83, 95% CI 1.05-3.35, P=0.032). A higher proportion of morphologically normal spermatozoa analysed under high magnification seem to carry the X chromosome. The aim of this study was to determine if the use of intracytoplasmic morphologically selected sperm injection (IMSI) is associated with gender incidence. Couples who underwent IVF with preimplantation genetic screening, as a result of advanced maternal age, were randomly allocated into two groups: intracytoplasmic sperm injection (ICSI; n=80) or intracytoplasmic morphologically selected sperm injection (IMSI; n=80). The incidences of genders were compared between ICSI- and IMSI-derived embryos. Our results showed that a significantly higher incidence of female embryos derived from IMSI compared with ICSI cycles (66.9% versus 52.5%, respectively, P=0.0322). This result was confirmed by logistic regression, which demonstrated a nearly 2-fold increase in female embryos derived from sperm selected by high magnification (OR 1.83, 95% CI 1.05-3.35, P=0.032). A higher proportion of morphologically normal spermatozoa analysed under high magnification seem to carry the X chromosome.


PubMed | Sapientiae Institute Educational and Research Center in Assisted Reproduction
Type: Journal Article | Journal: Archives of medical science : AMS | Year: 2012

Despite the fact that ovarian stimulation is controlled, it is not always predictable. Because the day of human chorionic gonadotrophin (hCG) injection depends mainly on the patients ovarian response to gonadotrophins, the day of oocyte retrieval cannot be determined in advance. As a result, oocyte retrievals are often scheduled to occur on weekends, a fact that entails at least one extra working day for the staff, and could lead to physical and psychological stress, especially in embryologists. The aim of this study was to evaluate whether intracytoplasmic sperm injection (ICSI) outcomes are influenced by the day of oocyte retrieval.A total of 327 ICSI cycles, whose retrievals were performed on Wednesdays and Sundays, were analysed in this retrospective study. Cycles were subdivided into two groups according to the day of oocyte retrieval: group W (n = 196), cycles in which oocyte retrieval was performed on Wednesday; and group S (n = 131), cycles in which oocyte retrieval was performed on Sunday. Groups were compared regarding fertilization, implantation, pregnancy and take-home baby rates.No significant differences were observed between groups A and B regarding fertilization rate (68.9% and 72.5%; p = 0.1589), implantation rate (21.8% and 24.3%; p = 0.5714), pregnancy rate (29.9% and 31.6%; p = 0.7129) and take-home baby rate (23.6% and 28.1%; p = 0.4351).A well-trained embryologists group adhering to staff scheduling allows large programmes to ensure a similar outcome independent of the workload or workday on which embryologists perform the manipulation of gametes.


PubMed | Sapientiae Institute Educational and Research Center in Assisted Reproduction
Type: Journal Article | Journal: Journal of assisted reproduction and genetics | Year: 2012

To evaluate if several genetic loci that are associated with variation in normal menopause age and early menopause can account for a poor response to controlled ovarian stimulation.A total of 71 patients age 35years old who were undergoing intracytoplasmic sperm injection were genotyped for four genetic variants that are associated with normal variation in menopausal age and early menopause. The patients were divided into two groups based upon treatment response: a poor responder group (PR group, n=21) and a normal responder group (NR group, n=50). The genetic variants rs244715, rs9379896, rs4806660 and rs16991615 were analyzed.There was no significant difference in the incidence of the genetic variants between the NR and PR group. The risk allele for the chromosome 19 variant (rs4806660) demonstrated a protective effect for a poor ovarian response. The presence of a risk allele was associated with an increased response to COS, which resulted in an elevated number of follicles (Coef: 2.54, P=0.041) and retrieved oocytes (Coef: 1.41, P=0.041).The genetic variants rs244715, rs9379896, rs4806660 and rs16991615 are not risk factors for poor ovarian response in Brazilian women. In contrast, rs4806660 is associated with higher number of follicles and retrieved oocytes. rs4806660 may be associated with an increased response to gonadotrophin stimulation in this population.

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