Técnica de doble disparo (doubble trigger) en pacientes normorrespondedoras con bajo porcentaje de ovocitos maduros / Doubble Trigger in patients with a normal response with a low percentage of mature oocytes

Resumen OBJETIVO: Evaluar el efecto del doble disparo en pacientes con un ciclo previo con menos de 65% de ovocitos maduros respecto de los ovocitos capturados, en una población con respuesta normal a la inducción de la ovulación con hCG recombinante o urinaria. MATERIALES Y MÉTODOS: Estudio de cohorte, prospectivo, efectuado en pacientes con diagnóstico de infertilidad, en tratamiento con fertilización in vitro, evaluadas en el Centro Mexicano de Fertilidad (Hospital Ángeles Lomas) entre 2017 y 2019. El tratamiento se llevó a cabo en la misma paciente, en cuyo ciclo previo convencional con esquema de antagonista e inducción de la ovulación con hCG tuvo respuesta ovárica subóptima y captura ovocitaria con menos de 65% en fase M2 (Grupo 1). Posteriormente se les indicó un segundo ciclo con el mismo esquema de gonadotropinas e inducción de la ovulación con doble disparo: acetato de triptorelina 1 mg + 5000 UI de hCG urinaria 40 y 34 horas previas a la captura (Grupo 2). Se evaluaron el porcentaje y la cantidad de ovocitos capturados en fase M2. RESULTADOS: Se registraron 34 pacientes en quienes se llevaron a cabo 68 ciclos. La cantidad de ovocitos capturados fue mayor en el grupo 2 (agonista de GnRH + hCG urinaria; p = 0.03). El doble disparo aumentó el porcentaje de ovocitos maduros (65.4 ± 21.3 vs 74.6 ± 20.2; p = 0.07). CONCLUSIONES: La técnica de doble disparo es valiosa para el tratamiento de pacientes con captura de ovocitos deficiente, aun con desarrollo folicular normal y concentraciones de estradiol adecuadas y óptimas de hCG el día de la captura. Se requieren estudios prospectivos de gran tamaño para dilucidar la recomendación mencionada de la técnica de "doble disparo".

Abstract OBJECTIVE: To evaluate the effect of double trigger in patients with a previous cycle with less than 65% of mature oocytes compared to the captured oocytes, in a normorresponding population with induction of ovulation with recombinant or urinary hCG. MATERIALS AND METHODS: A prospective cohort study, conducted in patients diagnosed with infertility, treated with in vitro fertilization, evaluated at the Mexican Fertility Center (Hospital Angeles Lomas) between 2017 and 2019. The treatment was carried out in the same patient, in whose previous conventional cycle with antagonist scheme and induction of ovulation with hCG had suboptimal ovarian response and oocyte capture with less than 65% in M2 phase (Group 1). Subsequently, a second cycle was performed with the same scheme of gonadotropins and induction of ovulation with double shot: 1 mg triptorelin acetate + 5000 IU of urinary hCG 40 and 34 hours prior to capture (Group 2 or double trigger). Percentage and quantity of oocytes captured in M2 phase were evaluated. RESULTS: 34 patients were registered, in whom 68 cycles were performed. The number of oocytes captured was greater in group 2 (agonist of GnRH + urinary hCG; p = 0.03). The double shot increased the percentage of mature oocytes 65.4 ± 21.3 vs 74.6 ± 20.2 (p = 0.07). CONCLUSIONS: The double trigger technique is valuable for the treatment of patients with poor oocyte capture, even with normal follicular development and adequate and optimal hCG estradiol concentrations on the day of capture. Large prospective studies are required to elucidate the aforementioned recommendation of the "double shot" technique.

[Assessment of progesterone levels on the day of the hCG administration as a predictor of success of antagonist stimulation protocols for IVF]. / Evaluación de la concentración de progesterona el día de la administración de hCG como predictor de éxito en protocolos de estimulación con antagonista para fertilización in vitro.

BACKGROUND: There are reports of deleterious effect when progesterone concentration is high during the follicular phase in cycles of in vitro fertilization. In our environment has not carried out a study to evaluate the pregnancy rate compared with progesterone concentration on the day of application of hCG. OBJECTIVE: To evaluate the pregnancy rate and outcome of in vitro fertilization cycle according to serum progesterone concentration on the day of application of hCG. MATERIAL AND METHODS: A retrospective, observational, cross-sectional study of 486 cycles of in vitro fertilization was done in the Centro Mexicano de Fertilidad of CEPAM (Hospital Angeles de las Lomas) from January 2009 to February 2014. We included all cases where it was used a stimulation protocol GnRH antagonist flexible scheme. RESULTS: When levels of progesterone are high, those of estradiol are also high and the number of retrieved oocytes and oocyte quality are lower. There was no difference in the percentage of fertilization, but at higher concentration of progesterone lower percentage of embryonic segmentation. Difference was recorded in the pregnancy rate only when progesterone concentration on the day of hCG application was > 4 ng/mL. CONCLUSION: Pregnancy rate decreases when the concentration of progesterone on the day of hCG application is ≥ 4 ng/mL.

[Effect of sexual abstinence on pregnancy rates after an intrauterine insemination]. / Efecto de la abstinencia sexual en las tasas de embarazo posterior a inseminación intrauterine.

BACKGROUND: There are many studies showing that more days of sexual abstinence increased sperm concentration, however, the direct influence between the days of abstinence and pregnancy rates has not been evaluated. The usual recommendation is 3-4 days prior to intrauterine insemination; this based on the interval that maximizes the number of motile sperm in the ejaculate. There are some reports with better success rate when abstinence is less than three days. OBJECTIVE: To evaluate the pregnancy rate post-intrauterine insemination according to days of sexual abstinence prior to obtaining semen sample. PATIENTS AND METHODS: A retrospective, observational and transversal study in patients attending the Mexican Center for Fertility (CEPAM) to intrauterine insemination. For analysis patients were grouped by age group, success rate and days of sexual abstinence. Continuous variables are reported as means and standard deviations; to determine statistical significance univariate logistic regression was performed. Categorical variables were evaluated in frequencies and percentages. The calculations were performed using JMP software program. RESULTS: 3,123 couples were included and increased success rate for intrauterine insemination was obtained with less than seven days of sexual abstinence. The rate of sperm retrieval is inversely proportional to the days of abstinence. CONCLUSION: A better pregnancy rate in intrauterine insemination was achieved with less than seven days of sexual abstinence and sperm retrieval rate was also recorded with fewer days of abstinence.

[Unselective single embryo transfer: chances of pregnancy related to operator experience]. / Transferencia no selectiva de embrón único: posibilidades de embarazo relacionadas con la experiencia del operador.

BACKGROUND: Selection of best quality embryo aims to achieve higher success rate, the pregnancy is unique and therefore obstetric risks are reduced. OBJECTIVE: To evaluate the pregnancy rate with no transfer of selected single embryo (TSSE) three days versus the experience of the physician performing the embryo transfer. PATIENTS AND METHODS: A retrospective, cross-sectional observational study in 159 patients Mexican Fertility Center in CEPAM protocol in vitro fertilization any indication, other ovulatory disorders and who was only possible obtain an embryo to be transferred in three day. For the analysis were grouped according to age, number of cells of the embryo transfer day and the doctor performed. Continuous variables are reported as means and standard deviations and univariate logistic regression was performed to determine statistical significance. Categorical variables were evaluated in frequencies and percentages. The calculations were performed with the software JMP. RESULTS: Protocol of single-embryo transfer not selected in three day pregnancy rate of 17% was obtained, with lower rates in women over 40 years of age and older embryos of more than 9 cells but also higher rate abortion. More experienced doctors achieved better pregnancy rates. CONCLUSION: This is the first study in Mexican population to assess the possibility of pregnancy with single embryo transfer in selected post-harvest with a three day success rate of 17% and first-order variables: number of cells on the day of transfer and experience of the physician who performed the procedure.

[The value of paternal age on the outcome of intrauterine insemination]. / El valor de la edad paterna en los resultados de inseminación intrauterina.

BACKGROUND: Although age to conceive has been delayed in both males and females, male age is controversial as decisive for this purpose. OBJECTIVE: To describe the results of intrauterine insemination pregnancy according to the age of the man. To determine whether this variable modifies semen parameters. To analyze whether pregnancy outcomes are modified by sperm morphology. PATIENTS AND METHODS: A descriptive, retrospective, longitudinal and analytical study. We analyzed 2,276 intrauterine insemination cycles performed in the Mexican Center for Fertility CEPAM from January 2000 to December 2012. We included only women under 35 years old without tubal occlusion. Semen parameters were evaluated after capacitation and the pregnancy rate by male age group and sperm morphology was analyzed. The results were analyzed with SPSS 20. Continuous variables were reported as means and their standard deviations and logistic regression univariate to determine the statistical significance. The categorical variables were evaluated in frequencies and percentages. RESULTS: 2,276 intrauterine insemination cycles were pooled according to the age of the male. The lower pregnancy rate was found in the group of men over 50 years. There was negative correlation between the increasing age with the total motile cell volume and morphology. There was only one pregnancy from a male over 50 years. When morphology was less than 4%, the pregnancy rate was significantly lower after 45 years; if it was more than 4% this effect was not observed. CONCLUSION: Male age affects pregnancy outcomes in intrauterine insemination cycles, as long as the sperm morphology is altered.

[Assisted hatching following embryo implantation failure]. / Eclosión asistida en pacientes con falla previa en la implantación embrionaria.

BACKGROUND: Assisted hatching in reproduction techniques has improved the successful implantation rates in certain groups of patients with poor prognosis. This study focuses on its effect in groups of patients with previous implantation failure and according to age groups. OBJECTIVE: Compare the pregnancy rates of patients who turned to this technique following an implantation failure using in vitro fertilization with those of patients who did not use assisted hatching before another attempt of in vitro fertilization and according to specific age groups. MATERIAL AND METHOD: Cases of patients using assisted hatching in our Center between January 2008 and December 2009 were studied. The results were compared in terms of age in three groups: group I, >35 years; group II, 35-39 years, and group III, > 40 years. RESULTS: Patients in group II had better pregnancy rate (30%) than those in groups I and III (16.98 and 20.83%, respectively). When comparing the results of the group of patients using assisted hatching with those of the group that did not, the first reported a 20% pregnancy rate versus no pregnancy in the other group.

[Comparative analysis of pregnancy rate/captured oocytes in an in vitro fertilization program]. / Análisis comparativo de la tasa de embarazo-ovocitos capturados en un programa de fertilización in vitro.

BACKGROUND: Since in vitro fertilization/embryo transfer is used as a common assisted reproductive technique there have been attempts to increase its success rate. One way is to obtain more good quality mature ovules to fertilize them, and two to three good quality embryos to transfer. OBJECTIVE: To determine if the number of retrieved oocytes is related with the pregnancy rate in IVF-ET. PATIENTS AND METHODS: Reproductive and descriptive study; 172 patients in the IVF program were included. Whole patients had ovary stimulation with FSHr and antagonist multidose protocol. Five study groups were considered depending on the oocyte number retrieved. Data were analized and correlated with fertilization and pregnancy rate. RESULTS: There were no statistical differences among age, body mass index, percentage of mature oocyte, fertilization rate, embryo cell stage or basal levels of LH and Estradiol. Group three showed the highest pregnancy rate (64.29%) nevertheless group five had major number of embryo transferred (2.97 +/- 0.54 vs 3.17 +/- 0.45, p = 0.21). According to FSH doses given, group one had statistical difference related to group three, with higher dose (54.1 vs 62.1). According to previous studies, related to the number of oocyte retrieved, the possibility of pregnancy is higher with more than 13 oocytes retrieved (OR: 0.9 IC 95%: 0.4 -1.7). CONCLUSIONS: Pregnancy rate is higher when ten to fifteen oocytes were retrieved.

[Clinical implication and frequency of the incidental finding of endometriosis during oocyte retrieval]. / Implicación clinica y frecuencia del hallazgo incidental de endometriosis durante la captura ovular.

BACKGROUND: Endometriosis is a clinical disease that is associated with poor outcomes in in vitro fertilization (IVF) programs with a decrease in oocyte retrieval, oocyte quality, implantation and pregnancy rates. When an endometrioma is diagnosed, it is indicated to remove endometrial cysts by laparoscopy or perform an aspiration before the cycle of IVF. OBJECTIVES: To evaluate the effect of endometriosis diagnosed incidentally during oocyte retrieval on the IVF outcome, as well as to establish its frequency. MATERIAL AND METHODS: Retrospective analysis of 1,000 files of patients who underwent to oocyte retrieval between January 2002 and March 2005, in the Centro Especializado para la Atenci6n de la Mujer in Mexico City. Of the total procedures tubal factor was the first indication for IVF and male factor was on second place. Only in seven patients of 1,000 oocyte retrievals was detected the presence of endometriosis fluid instead of folicular fluid. RESULTS: The prevalence of endometriosis diagnosed incidentally during oocyte retrieval was 0.7%, and the oocyte quality was 1.55 (regular). The fertilization rate for patients with endometriomas was 45% and the implantation and pregnancy rates were zero per cent while the patients without endometriomas the fertilization rate was 65% with an implantation rate of 18% and the pregnancy rate was 35%. CONCLUSION: Endometriosis is a disease that must be treated before an IVF cycle in stages III-IV and especially in presence of endometriomas because it could affect negatively IVF outcomes.

[Statistical and prognostic correlation of serum levels of basal inhibin to response and follicular quality in assisted reproduction]. / Correlación estadística y pronóstica de la concentración sérica de inhibina basal con la respuesta y calidad folicular en reproducción asistida.

BACKGROUND: Inhibin B is a direct marker of ovarian reserve and one of the earliest markers of ovarian aging. It has been used in assisted reproduction programs as a serum marker that can identify an altered follicular reserve and predict a good or poor response to the stimulation with exogenous gonadotropins. OBJECTIVE: To correlate inhibin B levels with follicular response and quality of oocytes obtained through ovarian stimulation controlled in an in vitro fertilization cycle (IVFET), as well as relate it with variables such as: fertilization percentage and pregnancy rates. PATIENTS AND METHODS: In a prospective and transversal study we included 71 patients that entered the IVFET program (February-April 2005). We determined inhibin B levels at the third day of the cycle and evaluated the follicular response and the oocyte quality during the ovarian stimulation, as well as fertilization and pregnancy rates. Statistical analysis was made with Spearman's and ANOVA tests. RESULTS: We observed a positive correlation between inhibin levels and quantity of developed follicles (0.457), number of captured oocytes (0.390), and quantity of metaphase II oocytes (0.324). We observed better oocyte quality in women with inhibin levels > 251 pg/ mL, and we considered that the ones that had levels < 50 pg/mL had poor follicular response (19.71%). There was no correlation with fertilization and pregnancy rates. CONCLUSIONS: In the early follicular phase inhibin B has direct correlation with ovarian reserve. Its high levels are related to better follicular response and oocyte quality. This enzyme levels are not useful as a predictive factor of pregnancy in IVFET cycles.

[Analysis of results of intrauterine insemination performed once or twice per stimulated cycle]. / Análisis de los resultados de la inseminación artificial realizada en una o dos ocasiones por ciclo estimulado.

OBJECTIVE: To compare double homologous versus only one intrauterine insemination (IUI) by stimulated cycle. PATIENTS AND METHOD: In a prospective, comparative study 138 patients were included, who underwent to intrauterine insemination; not inclusion parameters were: patients with cancelled cycles by poor response or by ovarian hyperestimulation syndrome risk. Patients were divided in two groups: Group 1 (N = 69) one insemination at 36 hours after human gonadotrophin chorionic hormone (hCG) and group 2 (N = 69) two inseminations 24 and 48 hours after hCG. Sperm separation was done with swim up, wash and resuspended or isolate techiques, and ovarian stimulation was done with recombinant FSH, menotrophins or clomiphene citrate. Statistical analysis was made by T Student and chi2 tests. RESULTS: The overall pregnancy rate was 13.04% per cycle; and seminal characteristics after seminal preparation were similar. We observed better pregnancy rates in the patients with ovulatory dysfunction and endometriosis (14.9% and 18.2%). No differences were established in pregnancy rates when patients were compared in function to seminal preparation. CONCLUSIONS: Double IUI at 24 and 48 hours after hCG has the same results in pregnancy rates than only one IUI correctly indicated 36 hours after hCG, but the costs increases in double insemination.

[Success' determinant variables in assisted reproduction]. / Variables determinantes del exito en la reproducción asistida.

OBJECTIVE: To perform a statistical analysis with variables that have influence on pregnancy rates to establish a prognostic factor of each one. PATIENTS AND METHODS: We performed a retrospective, descriptive, and observational study with 240 patients that underwent to IVF-ET program. The analyzed variables were: infertility factor, ovarian stimulation protocol, age of patients, basal hormonal levels, oestradiol preovulatory levels, endometrial characteristics, fertilization rate, number and quality of oocytes, number and quality of embryos, and difficulty of the embryo transfer. RESULTS: The mean age of the patients was 34 +/- 4.42 years old. Tubal and pelvic pathologies were the main infertility cause. During the statistical analysis we observed that the only variables with differences regarding pregnancy were the number of cells in the embryo (7.18 vs 5.9), the fertilization rate (58.3 vs 50.1%), and the number of transferred embryos. With the logistic regression analysis we observed that the number of cells on each embryo had a relative risk of 1.37 (CI 95%; 1.15-1.63), and that the number of transferred embryos had one of 1.63 (CI 95%; 1.10-1.58). CONCLUSIONS: There are many variables that influence the pregnancy rates, but with our results we consider that the embryo quality, its characteristics and the number of transferred embryos could predict better the possibilities of pregnancy in IVF-ET programs.

[Value of the morphological characteristics of polar body as a predictive factor of embryo development]. / Valor de las caracteristicas morfológicas del cuerpo polar como factor de predicción del desarrollo embrionario.

OBJECTIVE: To determine the relation between polar body quality and perivitelline space with fertilization and segmentation rates and embryo quality. STUDY: Prospective and descriptive. MATERIAL AND METHODS: Sixty-one patients underwent the in vitro fertilization and embryo transfer program (IVF-ET). The intracytoplasmatic sperm-injection (ICSI) was applied for insemination. Controlled ovarian hyperstimulation was made with recombinant FSH. Oocytes were evaluated 4-6 hours after retrieval and polar body, perivitelline space, and pellucid zone were assessed too. Fertilization was evaluated 17 hours after ICSI, and segmentation rates were analyzed at 48 and 72 hours. The number of blastomeres and quality of each embryo was assessed prior transference. Statistical analysis was done with chi2 test. RESULTS: We evaluated 883 oocytes, of which 43.8% had a normal polar body, 54.9% had a normal perivitelline space, and 69% a normal pellucid zone; 57% of retrieved oocytes with normal polar body developed an adequate fertilization rate, and oocytes with abnormal polar body had fertilization in less than 20%. Embryo cleavage was adequate in oocytes with normal polar body, in the abnormal oocytes was less than 20%, and 79% of the oocytes with fragmented polar body did not developed in embryo. There were not significant differences in fertilization rates and segmentation when compared with the pellucid zone and perivitelline space. CONCLUSIONS: Oocyte quality has a great influence on fertilization and embryo development. One of the most important variables is the polar body quality, which correlates adequately with fertilization and embryo cleavage.

Efecto de la albúmina humana en la movilidad y viabilidad espermática de muestras seminales preparadas para inseminación intrauterina / Effect of the human albumine in the spermatic mobility and viability inseminal samples for intrauterine isemination

Objetivo: Analizar el efecto de la albúmina humana sobre la viabilidad espermática. Material y métodos: Se procesaron por el método de swim-up 15 muestras de semen de sujetos sanos con semen normal (criterios de la OMS) utilizando HTF y HTF con albúmina humana al 10 por ciento, en alícuotas de la misma muestra. Al final de la preparación y a las 24 horas se midieron los parámetros de movilidad espermática utilizando el analizador automático Hamilton-Thorn IVOS 2000. Como medida de viabilidad se utilizó el índice de movilidad. Resultados: La velocidad en línea recta (VSL) disminuyó de 17.14 ñ 5.77 um/seg. (media ñ D.E.) a 12.21 ñ 3.86 um/seg, y 12.14 ñ 3.13 um/seg, en las muestras procesadas con y sin albúmina, respectivamente. A 24 horas de la preparación seminal, el IM disminuyó 11.41 por ciento en las muestras preparadas con albúmina y 21.75 por ciento en las muestras seminales que se prepararon con HTF sin albúmina (z = 1.88, p = 0.05). Los valores de la prueba hiposmótica obtenidos con el medio sin albúmina, fueron de 88.85 por ciento ñ 6.90 por ciento y con albúmina de 91.92 por ciento ñ 4.55 por ciento (p = 0.02). La integridad acrosomal también fue mayor en las muestras que se prepararon con albúmina (86.14 por ciento ñ 3.08 por ciento vs. 81.57 por ciento ñ 2.53 por ciento; p < 0.01). Conclusiones: Estos datos sugieren que la albúmina humana en el medio de preparación seminal, protege funcionalmente a los espermatozoides separados por swim-up y aumenta su sobrevida.