Preservación de la fertilidad: opinión de grupo de expertos en México / Fertility preservation: an expert taskforce opinion

La preservación de la fertilidad es la aplicación de estrategias médicas y de laboratorio para preservar la descendencia genética parental en adultos o niños en riesgo de esterilidad. El cáncer es la principal indicación de preservación de fertilidad en pacientes en edad reproductiva. En las últimas décadas ha incrementado la incidencia de cáncer en adolescentes. Los tratamientos oncológicos también han mejorado significativamente, por lo que hoy es posible la curación en un amplio porcentaje de pacientes. La mayoría de los niños y adolescentes con cáncer se convierten en sobrevivientes a largo plazo, lo que aumenta el interés en los efectos del tratamiento del cáncer sobre la fertilidad. Las condiciones sociales, económicas y culturales también son determinantes para decidir el momento que una pareja busque promover su fertilidad. Además, otras patologías o incluso fármacos para prevención del rechazo de órganos trasplantados pueden afectar la fertilidad y, por tanto, tales pacientes son susceptibles de orientación sobre preservación de la fertilidad. El éxito en los programas de reproducción asistida y en los tratamientos oncológicos brindan alternativas para preservar la fertilidad. En esta primera Opinión de Grupo de Expertos Mexicanos en Preservación de la Fertilidad hemos evaluado pacientes oncológicas que son candidatas a preservación de fertilidad: jóvenes con riesgo de compromiso de su fertilidad por el tratamiento oncológico, pero con reserva ovárica suficiente y pronóstico vital aceptable. También se consideraron casos especiales como la preservación social, en casos de conceptualización sexual diferente, así como los aspectos legales y éticos básicos

Fertility preservation is the application of medical and laboratory strategies to preserve parental genetic offspring in adults or children at risk of sterility. Cancer is the main indication of fertility preservation in patients of reproductive age. In recent decades, the incidence of cancer in adolescents has increased. Cancer treatments have also improved significantly, making cure possible today in a large percentage of patients. Most children and adolescents with cancer become long-term survivors, increasing interest in the effects of cancer treatment on fertility. Social, economic and cultural conditions are also decisive in deciding when a couple seeks to promote their fertility. Furthermore, other pathologies or even drugs for the prevention of rejection of transplanted organs can affect fertility and, therefore, such patients are susceptible to guidance on fertility preservation. Success in assisted reproduction programs and cancer treatments provide alternatives to preserve fertility. In this first Opinion of the Group of Mexican Experts on Fertility Preservation, we have evaluated oncological patients who are candidates for fertility preservation: young people at risk of compromising their fertility due to oncological treatment, but with sufficient ovarian reserve and acceptable vital prognosis. Special cases such as social preservation were also considered, in cases of different sexual conceptualization, as well as the basic legal and ethical aspects

[Influence of the high peak serum estradiol on the outcome of in vitro fertilization cycles]. / Influencia de las concentraciones séricas de estradiol en el resultado de ciclos de reproducción asistida in vitro.

BACKGROUND: For the use of assisted reproductive technologies of high complexity (IVF-ET and ICSI) is essential to proper ovarian stimulation with recombinant FSH drugs menotropins, as well as the use of GnRH analogues. OBJECTIVE: To correlate serum estradiol level on day 10th with the outcome of in vitro fertilization cycles. MATERIAL AND METHOD: Retrospective study of 523 IVF cycles, selected and analyzed from 2005 to 2009. Patients underwent individualized stimulation protocols with gonadotropins and agonist (late luteal phase). The patients were divided into three groups according with the serum level of estradiol on day 10th of stimulation: Group I, patients with serum level of Estradiol below 1,000 pg/mL; Group II, with levels between 1,000-4,000 pg/mL; and Group III, with levels above 4,000 pg/mL. Peak serum estradiol levels, oocyte number, fertilization rates, implantation rates, and pregnancy rates were compared among groups. RESULTS: The fertilization rate was 62.8 in Group I; 60.6% in Group II, and 54.2% in Group III. The pregnancy rate in Group I was 29.8%; in Group II, 37.3%; and 24% for Group III. The implantation rates were 14, 22 and 14% for each group respectively (I, II and III). CONCLUSIONS: There is an inverse relationship between high peak serum estradiol levels and pregnancy rate; the implantation rate seems affected by the extreme levels of serum estradiol. The percent of total mature oocytes and fertilization rate improve with serum levels of estradiol at physiologic values.

[Intacytoplasmic sperm injection: reproductive reality in couples with sterility]. / Inyección intracitoplasmática de espermatozoides: realidad reproductiva en la pareja con esterilidad.

BACKGROUND: The intacytoplasmic sperm injection (ICSI) is the assisted reproduction technique (ART) that currently offers satisfactory results to infertile couples. The use of epididymal surgical retrieval (percutanean epydidimal sperm aspiration: PESA) and testicular sperm retrieval (testicular sperm extraction: TESE) combined with ICSI has come to bring a high response to azoospermic male. OBJECTIVE: To communicate the results obtained from the Institute for the Study of Human Conception, in Monterrey, NL, with the application of the ICSI technique with ejaculate sperm and in azoospermic patients using sperm obtained from PESAor by testicular sperm extraction TESE. METHODS: From January 1999 to December 2003 1,436 couples were studied at the Institute for the Study of Human Conception, Monterrey, Mexico; 729 cases underwent to ICSI (50.8%), 670 used the ejaculate sperm, in 37 cases (5%) PESA and 22 cases (3%) TESE. These patients were treated as usual: controlled ovarian hyperstimulation (COH) with FSHr alone or combined with HMG or LHr, use of GnRH analogs (agonist o antagonist), follicular monitoring up to the presence of 3 follicles longer than 18 mm; ovular retrieval 34 h after HGC application and embryo transfer in days 3 or 5 of development. RESULTS: No statistically significant difference was noted in the woman's age (p = 0.623), type and time of sterility (p = 0.446, 0.150), neither in FSH, LH and estradiol levels (p = 0.549, 0.623, 0.685). The middle age of the male had significant difference between PESA (38.9 +/- 7.3) and ejaculated sperm (36.1 +/- 6.4) (p = 0-024). The pregnancy rates among groups of the ejaculate sperm, PESA and TESE were 32.8%, 43.2% and 40.9% respectively, without significant difference (p = 0.327), neither in implantation rates: 11.2%, 26% and 11%, respectively (p = 0.153). CONCLUSIONS: The technique of ICSI and use of PESA and TESE offer satisfactory results in infertile couples, including azoospermic male.

[Endometrial thickness. Prognostic factor in assisted reproduction?]. / Grosor endometrial y predicción del embarazo en reproducción asistida.

BACKGROUND: Most authors coincide that an endometrial thickness lesser than 8 mm has a very low pregnancy rate. OBJECTIVE: To determine if the measurement of endometrial thickness by vaginal ultrasound has a prognostic value over the pregnancy rate in patients with endometrial preparation for an embryo transfer in cycles of frozen embryos and ovum donation. STUDY DESIGN: Retrospective and comparative. MATERIAL AND METHODS: A total of 100 cycles were analyzed in the group of frozen embryo transfer; and 71 cycles in the group of ovum donation, we subdivided these two groups into two more groups, one with an endometrial thickness of 8 mm or less and the other with more than 8 mm. RESULTS: There is a significant difference in the group of frozen embryo transfer regarding the age of the patients (p = 0.009). The pregnancy rate in the group of frozen embryo transfer with an endometrial thickness of 8 mm or less was 14.7% and of 37% in the group with more than 8 mm, with a significant difference (p < 0.01). When we analyzed the cycles of ovum donation, we did not found a significant difference, and we found a pregnancy rate of 47% in the group with endometrial thickness of 8 mm or less, and 40% in the other group. CONCLUSION: In the present study we found that the measurement of the endometrial thickness of more than 8 mm in the patient undergoing a frozen embryo transfer has a predictor value.

[Comparison of GnRH agonists and antagonists in an ovular donation program]. / Comparación de agonistas y antagonistas de GnRH en un programa de donación ovular.

INTRODUCTION: GnRH agonists and antagonists are utilized for avoiding premature ovulation in assisted reproductive cycles, (ART) this retrospective study was designed to compare both treatments in controlled ovarian hyperstimulation (HOC) in oocyte donors. MATERIAL AND METHODS: Between Jan99 and Mar03, 141 oocyte donors underwent ART receiving either 0.25 mg daily of a GnRH antagonist (Cetrorelix) from day 6 of stimulation (51 patients) or a long protocol with a GnRH agonist (Leuprolide acetate) (90 patients.) FSHr alone or with HMG or LHr were employed for ovarian stimulation. hCG (Profasi, Serono) was administrated when more than three follicles above 18 mm in diameter were observed, oocyte retrieval was performed 34 hours later. Embryo transfer was performed 3-5 days later. RESULTS: Both groups were homogeneus for age (p=0.142), day 3 FSH (p=0.115), type and total dose of gonadotrophins utilized. There were no significant differences in follicles number (p=0.522), oestradiol levels on the day of hCG (p=0.310) and fertilization rates (p=0.177) The mean number of oocytes retrieved and metaphase II oocytes was significantly lower in GnRH agonist group, (12 vs. 13.9, p=0.05 and 8.6 vs 11; p=0.007) There was no statistical differences in pregnancy and implantation rates between agonist and antagonist groups (52.2% vs 60.8%, 15.1% vs 18.3%; p=0.327 and 0.652). CONCLUSIONS: The high number of metaphase oocytes and the high pregnancy rate observed in the oocyte donors provide evidence that GnRH antagonist does not impair ovarian response, embryo quality or pregnany rates. In oocyte donors cycles the GnRH antagonist is a valid alternative to GnRH agonist, providing the benefit of more flexibility in patient's scheduling.

[Influence of sperm morphology on results of intrauterine insemination]. / Influencia de la morfología espermática en los resultados de inseminación intrauterina.

OBJECTIVE: To determine the influence of sperm morphology, according to WHO criteria, on pregnancy rates of couples who were submitted to intra-uterine insemination (IUI). MATERIAL AND METHODS: Retrospective study that included 787 IUI cycles performed in the Instituto para el Estudio de la Concepción Humana in Monterrey, Mexico, from January to December 2002. Main diagnosis were anovulation, male factor, endometriosis, and cervical factor. All patients were allocated into a controlled ovarian hyperstimulation protocol with either clomiphene citrate, menotropins and/or recombinant FSH. RESULTS: A total of 115 pregnancies were achieved (pregnancy rate per cycle of 14.61%). When seminal parameters were analyzed as independent factors it was found that a motility less than 10%, total motile count after sperm preparation less than 1 million/ml and sperm motility less than 20% had a pregnancy rate of zero. CONCLUSIONS: Patients with normal sperm forms less than 20% according to WHO criteria have no benefit with the IUI and these patients should be canalized to ART.

[Comparison of the results of an assisted-reproduction program related with the day of follicular aspiration]. / Comparación de los resultados de un programa de reproducción asistida relacionados con el día de aspiración folicular.

UNLABELLED: The proper time for the oocyte retrieval allow us to obtain good quality oocytes In assisted reproduction techniques, improving fertilization and pregnancy rates. The follicular aspiration has been done by vaginal ultrasounds when we can see at least 3 follicles > or = 16 mm diameter. OBJECTIVE: To compare oocyte quality, fertilization and pregnancy rate-according to the day of the follicular aspiration. MATERIAL AND METHODS: 438 cycles were studied in the Instituto para el Estudio de la Concepción Humana in Monterrey Mexico, comparing oocyte quality, fertilization and pregnancy rate. RESULTS: If egg retrieval was done on day 12 of the cycle, we obtained a mean of 7.61 good quality oocytes, 51% of them fertilized and the pregnancy rate was 36.8%, when the aspiration was performed on day 13 of the cycle, we obtained a mean of 7 good quality oocytes, 59% of them fertilized and the pregnancy rate was 34%, and if the oocyte retrieval was on day 14 of the cycle, we obtained a mean of 6.42 good quality oocytes, 57% of the fertilized and the pregnancy rate was 31.7%. DISCUSSION: The oocyte quality, fertilization and pregnancy rate were slightly better if the oocyte retrieval was performed on day 12 or 13 of the cycle, rather than day 14. However this was no statistical significative.

[Methodology in gynaecological clinical research]. / Metodología de investigación clínica en Ginecología.

Every day the number of published articles in the world wide literature is increased; unfortunately, lot of them lack of a proper research-related methodology and therefore the conclusions might be of less scientific value. Clinicians need to develop their professional exercise based on scientific knowledge and so it is imperative to be familiar with research-related methodology. The present paper offers some tips in order to facilitate the reading and correct interpretation of clinical research.

[Prognostic values of oestradiol/oocyte rate in ICSI patients]. / Pronóstico del indice estradiol-ovulo en la inyección intracitoplasmática de espermatozoides (ICSI).

OBJECTIVES: To analyze the pregnancy rate in women who underwent Intracytoplasmic Sperm Injection (ICSI) program depending of the oestradiol/oocyte index. STUDY DESIGN: Retrospective, comparative. MATERIAL AND METHODS: 332 patients were included. There were divided in three groups depending on the oestradiol/oocyte index: Group A:(100 pg/mL, group B: 101-250 pg/mL and group C: > 250 pg/mL). Therapeutic protocol. Down regulation with leuprolide acetate in late luteal phase protocol, COH with rec-FSH and / or HMG, ultrasonographic and estradiol blood levels were monitored; hCG application when > 3 follicles > 18 mm, oocyte retrieval performed 34 hours later. We analyzed: patient age, male age, number of follicles, estradiol serum levels at the day of hCG application, number of mature oocytes, oestradiol/oocyte index, fertilization rate, transferred embryos, transfer quality, catheter type and luteal support. Statistical analysis (SPSS 11) with chi square, ANOVA and Kruskall-Wallis was used. RESULTS: On having analyzed the number of metaphase II oocytes retrieval, oocytes fertilized and number of transferred embryos among three groups, the best results were obtained in group B. The differences among these variables were significant. (P = 0.014, p = 0.005 and p = 0.003, respectively). When the oestradiol/oocyte index was analyzed and the PR among groups (21.83, 36.62 and 17.80 %) we observed a significant difference (p = 0.003). CONCLUSION: It is convenient to monitor the oestradiol blood levels to offer schemes of COH less aggressive to improve the oocyte quality. The oestradiol/oocyte index is a parameter adapted as a predictive value of pregnancy.

[High concentrations of serum estradiol in assisted reproduction]. / Altas concentraciones de estradiol sérico en reproducci6ón asistida.

OBJECTIVES: To analyze the influence of the levels of estradiol on the day of HCG in the pregnancy rate (PR) of ICSI and oocyte donation. STUDY DESIGN: Retrospective, comparative. MATERIAL AND METHODS: 333 patients underwent ICSI and 66 in oocyte donation were included dividing them according to the level of estradiol: a) < 1,000 pg/mL, b) 1,001-3,000 pg/mL and c) > 3,000 pg/mL. Therapeutic protocol: Down regulation with acetate leuprolide in late luteal phase, COH with FSHr and/or HMG, ultrasonographic monitoring and estradiol blood levels, HCG application with > 3 follicles > 18 mm, oocyte retrieval 34 hours later. We analyzed: PR, age (including receptors), FSH and LH. Number, mature grade and fertilized oocytes; luteal support, transfer quality and type of catheter. Statistical analysis (SPSS 11) with chi square, ANOVA and Kruskall-Wallis. RESULTS: ICSI: Older patients in group A (p < 0.001), but without difference between B and C groups (p = 0.08). Statistical difference in number of follicles, number of oocytes, fertilized oocytes and transferred embryos being less in the A group (p < 0.001). Statistical difference in PR 21.7, 35.6 and 25.7% in A, B and C groups respectively (p = 0.032). Oocyte donation: Group A has younger patients (p = 0.005), FSH and LH were similiar among groups. Major number of follicles were observed to increase estradiol levels, but major quantity of metaphase II and fertilized oocytes were observed in group B (p = 0.05). PR without significant differences: 50, 51.5 and 52.3% in groups A, B and C (p = 0.977). Without statistical difference in the age of receptors; transferred embryos, type of catheter and quality on ICSI and oocyte donation groups. CONCLUSION: High estradiol levels at the day of HCG application affect the PR in patients submitted to ICSI. The best results were obtained with estradiol levels between 1,000 and 3,000 pg/mL. In oocyte donation the high concentrations of estradiol do not affect the PR of the receptors.

[Vaginal misoprostol in the prevention of postpartum hemorrhage]. / Misoprostol vaginal para la prevención de la hemorragia posparto.

OBJECTIVE: To show the advantages of the use of vaginal misoprostol, a prostaglandine E1 analogue, in the prevention of the post-partum haemorrhage. MATERIAL AND METHODS: This was a prospective, observational, comparative study. The study included 400 patients with high risk of postpartum haemorrhage at our center between January 1999 and may 2001. Patients were divided in two groups. In group I (208 patients) misoprostol was used in a dose of 800 ugr and in group II (192 patients) in whom misoprostol was not used. Both groups were treated initially with our conventional oxytocin protocol. We evaluated the use of additional oxytocin or ergotamine, haemoglobin levels pre and post-partum, the amount of blood loss, and the need for blood transfusion or hysterectomy. RESULTS: The need for additional oxytocin or ergotamine was reduced to less than 10% in group I when compared to group II; the drop in haemoglobin levels and the amount of blood loss were also less in group I (p: 0.03). In this group only one patient needed for blood transfusion and no patient needed hysterectomy. In group II six patients need a blood transfusion and there was the need for two hysterectomies. CONCLUSION: The use of vaginal misoprostol is effective to control the postpartum bleeding, reducing the blood loss after birth in women with high risk of post-partum haemorrhage as well as the need for blood transfusion. It's use has mild side effects and is of low cost.