Trisomy 21 and Assisted Reproductive Technologies: A review.

Trisomy 21 is the most common genetic disorder seen among infants, and it causes spontaneous abortions, abnormal neural development and other pathologies associated with newborn development. In newborns with this trisomy, 90-95% have full trisomy, 1.4-1.9% have mosaicism, and 1-4.7% have translocations. The principal cause of trisomy 21 is advanced maternal age, in which recombination errors may occur during fetal development, age-related accumulation of damaged DNA, cohesin degradation producing the premature loss of chromosomes or sister chromatids, and alterations during the spindle formation process. The paternal age has also an effect on trisomy 21, specifically during male aging, when there is higher risk of chromosomal breaking in spermatozoa. Epigenetics is also an important risk factor of trisomy 21 through changes in the DNA methylation process, histone modification and non-coding RNAs. Assisted reproductive technologies (ART) have emerged in recent years as a safe alternative for couples with fertility problems. These techniques, which include controlled ovarian stimulation (COS), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and vitrification, decrease the incidence of aneuploidy in human preimplantation embryos, and are widely used. The following study aims to review and discuss the available literature on trisomy 21 in the field of assisted human reproduction.

Overweight and obesity significantly reduce pregnancy, implantation, and live birth rates in women undergoing In Vitro Fertilization procedures.

OBJECTIVE: The objective of this study was to evaluate the effects of overweight and obesity on fertility outcomes in IVF procedures. METHODS: This was a retrospective and nonrandomized study that included 191 IVF/ICSI cycles using non-donor oocytes performed between July 2016 and December 2018 that were allocated according to Body Mass Index (BMI) in three groups: Normal group: 18.5-24.9 (n=67 women), Overweight group: 25.0-29.9 (n=86 women) and Obesity group: ≥30.0 (n=38 women). We compared fertilization rates, embryo quality at day 3, development and quality of blastocyst, pregnancy rates, implantation rates, and live birth rates. RESULTS: Patients from all groups had similar stimulation days, but those women with overweight and obesity used more hormones compared to women with normal weight (p<0.05). Fertilization rates, zygotes that underwent cleavage and good-quality embryos at Day 3 were similar between the three evaluated groups. The groups of overweight and obesity had embryos at Day 3 with significantly less cells, compared to those from the normal group (p<0.05). The blastocyst development rate was significantly lower in women with overweight and obesity compared to women with normal BMI (p<0.05); but, the percentages of good blastocysts were similar in all studied patients. Pregnancy, implantation and live birth rates were significantly lower in the group of women with overweight and obesity, compared to those women with normal weight (p<0.05). Obese women had significantly more miscarriages compared to those in the other groups (p<0.05). CONCLUSIONS: Our data shows that an increased BMI affects embryo development and significantly reduces the pregnancy, implantation and live birth rates.

High percentages of embryos with 21, 18 or 13 trisomy are related to advanced paternal age in donor egg cycles.

OBJECTIVE: Advanced paternal age is related to poor sperm quality; however, little is known on its effect on aneuploidy embryo rates and, more importantly, on chromosomal abnormalities like trisomy 21, 18 and 13. The objective of this study was to evaluate the effect of advanced paternal age on the trisomy rates of the chromosomes 21, 18 or 13 in embryos obtained from donated oocytes. METHODS: A total of 378 embryos, obtained from 52 IVF/ICSI cycles with donated oocytes in conjunction with PGD, were allocated according to paternal age in three groups: Group A: ≤39 years (n=115 embryos), Group B: 40-49 years (n=157 embryos) and Group C: ≥50 year (n=106 embryos). Fertilization rates, embryo quality at day 3, blastocysts development, and aneuploidy embryo rates were then compared. RESULTS: There was no difference in seminal parameters (volume, concentration and motility) in the studied groups. Fertilization rate, percentages of zygotes that underwent cleavage, and good-quality embryos on Day 3 were similar between the three groups evaluated. The group of men ≥50 years had significantly more sperm with damaged DNA, higher global aneuploidy rates, and significantly more embryos with trisomy 21, 18 or 13 compared to the other two evaluated groups (p<0.05). CONCLUSIONS: Our data shows that advanced paternal age increases global chromosomal abnormalities, and percentages of trisomy 21, 18 or 13 in embryos, and such effect is significantly important as of the age of 50. Embryo genetic screening is highly recommended in patients in which paternal age is ≥50 years old.

Ectopic ovarian pregnancy after intracytoplasmic sperm injection with testicular spermatozoa - a case report.

Ovarian ectopic pregnancy is a rare event in both natural and assisted human reproduction settings. There are few reports of this event after in vitro fertilization. Diagnosis can be challenging, since it requires specific medical expertise. Patients with this condition call for careful management during treatment so as to not affect their fertility potential. This paper describes the case of a woman submitted to ICSI and embryo transfer who subsequently had an ovarian ectopic pregnancy and underwent a laparoscopic partial right oophorectomy.

High Aneuploidy Rates Observed in Embryos Derived from Donated Oocytes are Related to Male Aging and High Percentages of Sperm DNA Fragmentation.

CAPSULE: Male aging effects on aneuploidy rates in embryos. OBJECTIVE: Paternal age is associated with decreasing sperm quality; however, it is unknown if it influences chromosomal abnormalities in embryos. The objective of this study is to evaluate if the aneuploidy rates in embryos are affected by advanced paternal age. METHODS: A total of 286 embryos, obtained from 32 in vitro fertilization/intracytoplasmic sperm injection cycles with donated oocytes in conjunction with preimplantation genetic diagnosis, were allocated according to paternal age in three groups: Group A: ≤39 years (n = 44 embryos); Group B: 40-49 years (n = 154 embryos); and Group C: ≥50 years (n = 88 embryos). Fertilization rates, embryo quality at day 3, blastocyst development, and aneuploidy embryo rates were then compared. RESULTS: There was no difference in the seminal parameters (volume, concentration, and motility) in the studied groups. Fertilization rate, percentages of zygotes underwent cleavage, and good quality embryos on day 3 were similar between the three evaluated groups. The group of men ≥50 years had significantly more sperm with damaged DNA, low blastocyst development rate, and higher aneuploidy rates in embryos compared to the other two evaluated groups (P < 0.05). CONCLUSIONS: Our findings suggest that advanced paternal age increases the aneuploidy rates in embryos from donated oocytes, which suggests that genetic screening is necessary in those egg donor cycles with sperm from patients >50 years old.

The IMSI Procedure Improves Laboratory and Clinical Outcomes Without Compromising the Aneuploidy Rate When Compared to the Classical ICSI Procedure.

PURPOSE: The intracytoplasmic morphologically selected sperm injection (IMSI) procedure has been associated with better laboratory and clinical outcomes in assisted reproduction technologies. Less information is available regarding the relationship between embryo aneuploidy rate and the IMSI procedure. The aim of this study is to compare the clinical outcomes and chromosomal status of IMSI-derived embryos with those obtained from intracytoplasmic sperm injection (ICSI) in order to establish a clearer view of the benefits of IMSI in infertile patients. METHODS: We retrospectively analyzed a total of 11 cycles of IMSI and 20 cycles of ICSI with preimplantation genetic diagnosis. The fertilization rate, cleavage rate, embryo quality, blastocyst development, aneuploidy rate, pregnancy rate, implantation rate, and miscarriage rate were compared between the groups. RESULTS: Similar rates of fertilization (70% and 73%), cleavage (98% and 100%), and aneuploidy (76.9% and 70.9%) were observed in the IMSI and ICSI groups, respectively. The IMSI group had significantly more good quality embryos at day 3 (95% vs 73%), higher blastocyst development rates (33% vs 19%), and greater number of hatching blastocysts (43% vs 28%), cycles with at least one blastocyst at day 5 (55% vs 35%), and blastocysts with good trophoectoderm morphology (21% vs 6%) compared with the ICSI group (P < 0.001). Significantly higher implantation rates were observed in the IMSI group compared with the ICSI group (57% vs 27%; P < 0.05). Pregnancy and miscarriage rates were similar in both groups (80% vs 50% and 0% vs 33%, respectively). CONCLUSION: The IMSI procedure significantly improves the embryo quality/development by increasing the implantation rates without affecting the chromosomal status of embryos. There is a tendency for the IMSI procedure to enhance the pregnancy rates and lower the miscarriage rates when compared with ICSI.

In Vivo Culture System Using the INVOcell Device Shows Similar Pregnancy and Implantation Rates to Those Obtained from In Vivo Culture System in ICSI Procedures.

CAPSULE: Clinical outcomes using INVOcell device with ICSI. OBJECTIVE: Intravaginal culture of oocytes (INVO) procedure is an intravaginal culture system that utilizes the INVOcell device in which the fertilization and embryo culture occur. In this procedure, the vaginal cavity serves as an incubator for oocyte fertilization and early embryonic development. The objective of this study was to evaluate the clinical outcomes of this intravaginal culture system in intracytoplasmic sperm injection (ICSI). METHODS: A total of 24 cycles INVO-ICSI (study group) and 74 cycles of ICSI (control group) were included in the study. The cleaved oocytes at day 3/total injected oocytes, embryo quality, pregnancy rate (PR), implantation rate (IR), and miscarriage rate (MR) were compared between both groups. RESULTS: At day 3, there was no difference in the cleaved oocyte rate (78.7 and 76.1%) and embryo quality (77 and 86.8%) for the study and control groups, respectively. In the study group, more embryos were significantly transferred compared to the control group (2.63 ± 0.58 versus 1.93 ± 0.25; P < 0.05). PRs, IRs, and MRs were similar for the study group compared with the control group (PR: 54.2% versus 58.1%; IR: 31.7% versus 33.6%; MR: 7.7% versus 20.9%). CONCLUSIONS: Good PR and IR can be obtained using the INVOcell device, and the INVO-ICSI procedure can be considered as an alternative option to infertile patients.

Tasa de Blastulación en función del número de ovocitos en metafase II / The Percentage of Blastulation as function in the number of metaphase II oocytes

OBJETIVOS: Determinar el número de ovocitos en metafase II que se necesitan para lograr una óptima tasa de blastulación y conseguir una mejor tasa de gestación. DISEÑO: Estudio Retrospectivo. Institución: Unidad de Fertilidad -Hospital Alcivar Guayaquil (Ecuador). PARTICIPANTES: Mujeres con diagnóstico de infertilidad. INTERVENCIONES: Fueron 110 Mujeres en las que se les realizo FIV-ICSI, excluyendo transferencia día 3 y ciclos cancelados. previa estimulación ovárica controlada, El cultivo continúa a blastocistos. Principales medidas de resultados: Tasa de ovocitos en metafase II, Tasa de embarazo. Edad Promedio de las pacientes, Técnica FIV-ICSI. RESULTADOS: Edad promedio de las pacientes 33,41. Técnica FIV: 73 pacientes 66,4 % ICSI: 37 pacientes 33,6 %. Embarazo: Si Gestación: 57,3 %, No gestación: 42,7 %. Tasa de Ovocitos en Metafase II: Una Media de 7,5. CONCLUSIÓN: La tasa de gestación que coincide con los resultados del centro (50 a 60 %), la alcanzamos a partir de 7 ovocitos maduros. La tasa de blastulacion promedio fue de 39,2 %

OBJECTIVES: Determine the number of metaphase II oocytes that are needed for optimum rate blastulation and get a better rate of gestation. DESIGN: Retrospective study. Institution: Fertility Unit -Hospital Alcivar Guayaquil (Ecuador). PARTICIPANTS: Women diagnosed with infertility. INTERVENTIONS: There were 110 women in which they are performed IVF-ICSI, excluding 3rd and transfer canceled cycles. After controlled ovarian stimulation, cultivation continues to blastocysts. Main outcome measures: Rate of metaphase II oocytes, pregnancy rate. Average age of patients, IVF-ICSI technique. RESULTS: Mean age of the patients 33,41. IVF technique: 66.4% ICSI 73 patients: 37 patients 33.6%. Pregnancy: If pregnancy: 57.3% No pregnancy: 42.7% .Tasa of oocytes in metaphase II: A Media 7.5. CONCLUSION: The pregnancy rate coincides with the center's results (50-60%), the reach from 7 mature oocytes. The average rate was 39.2% blastulation

Percentage of Blastulation on the Number and Function of Metaphase II Oocytes.

OBJECTIVE: Establish the number of metaphase II oocytes that are needed for optimum blastulation rate and to achieve a better rate of gestation. METHODS: Retrospective study. Women diagnosed with infertility. There were 110 women submitted to IVF/ICSI, excluding third day transfers and those with canceled cycles. After controlled ovarian stimulation, cultivation continued to blastocysts. RESULTS: Average age of the patients: 33.41. IVF technique: 73 patients, 66.4%; ICSI: 37 patients, 33.6%. Pregnancy: gestation: 57.3%; Non-gestation: 42.7%. Mean number of oocytes in metaphase II: 7.5. CONCLUSION: The gestation rate coincides with the center's results (50-60%), reached with 7 mature oocytes. Mean blastulation rate was 39.2%.

Niveles séricos de testosterona y estradiol y su relación con la saturación arterial de oxígeno (SaO2) en mujeres pre y post-menopausicas de nivel del mar y altura

El presente estudio fue diseñado para determinar la asociación de los niveles séricos de Testosterona (T) y Estradiol (E2) y la relación T/E2 con la Saturación Arterial de Oxígeno (SaO2) en 247 mujeres pre y post-menopáusicas del nivel del mar y altura. Los valores de la Testosterona y Estradiol séricos fueron medidos por radioinmunoensayo (RIA); los valores de la hormona folículo Estimulante (FSH) se determinaron por ensayo inmunoradiométrico (IRMA). Se han establecido dos grupos de estudio en base a la presencia o ausencia de ciclos menstruales: mujeres premenopáusicas y post-menopáusicas, tanto a nivel del mar y altura. la mujeres post-menopáusicas del nivel del mar y altura presentaron de maneras significativas menores niveles de T, E2 y mayores de FSH en relación a las pre-menopáusicas de ambas poblaciones. La concentracción sérica de T, E2 y FSH fue similar entre menopáusicas de nivel del mar y de altura; lo mismo fue observado para el caso de las post-menopáusicas. La relación T/E2 fue significativamente mayor en mujeres post-menopáusicas de ambas poblaciones en relación a las pre-menopáusicas. La relación T/E2 > 20 en la altura se encuentra asociada con una disminución significativa en la Saturación Arterial de Oxígeno y un incremento del hematocrito. Si la relación T/E2 es <20 no se afecta el hematocrito. Una relación T/E2 >20 se encuentra en mayor proporción durante la menopausia. El coeficiente de correlación entre la relación Testosterona/Estradiol y la Saturación Arterial de Oxígeno fue de r=0.46 (P<0.01) y el coeficiente de regresión lineal fue de - 0.31ñ0.29 (ßñES)(P<0.001) los resultados del presente estudio indican que los bajos niveles de SaO2 observado en mujeres post-menopáusicas de la altura podrían tener relación con los altos valores de la relación Testosterona /Estradiol.