Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial

Objective To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF. Design Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1). Setting Reproductive medicine clinics. Patient(s) A total of 1,329 women (aged 18â40 years). Intervention(s) Follitropin delta (AMH <15 pmol/L: 12 μg/d; AMH â¥15 pmol/L: 0.10â0.19 μg/kg/d; maximum 12 μg/d), or follitropin alfa (150 IU/d for 5 days, potential subsequent dose adjustments; maximum 450 IU/d). Main Outcomes Measure(s) Ongoing pregnancy and ongoing implantation rates; noninferiority margins â8.0%. Result(s) Ongoing pregnancy (30.7% vs. 31.6%; difference â0.9% [95% confidence interval (CI) â5.9% to 4.1%]), ongoing implantation (35.2% vs. 35.8%; â0.6% [95% CI â6.1% to 4.8%]), and live birth (29.8% vs. 30.7%; â0.9% [95% CI â5.8% to 4.0%]) rates were similar for individualized follitropin delta and conventional follitropin alfa. Individualized follitropin delta resulted in more women with target response (8â14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH <15 pmol/L) (11.8% vs. 17.9%), fewer excessive responses (â¥15 or â¥20 oocytes in patients with AMH â¥15 pmol/L) (27.9% vs. 35.1% and 10.1% vs. 15.6%, respectively), and fewer measures taken to prevent ovarian hyperstimulation syndrome (2.3% vs. 4.5%), despite similar oocyte yield (10.0 ± 5.6 vs. 10.4 ± 6.5) and similar blastocyst numbers (3.3 ± 2.8 vs. 3.5 ± 3.2), and less gonadotropin use (90.0 ± 25.3 vs. 103.7 ± 33.6 μg). Conclusion(s) Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation. Clinical Trial Registration Number NCT01956110

Falência ovariana precoce associada a deleção no braço longo do cromossomo: relato de dois casos e revisão da literatura Premature ovarian failure with a deletion in the long arm of chromosome: report of two cases and review of the literature

Falência ovariana prematura pode ser idiopática ou estar associada a várias distúrbios auto-imunes ou genéticos, como as deleções do cromossomo X. Relatamos dois novos casos de deleções do braço longo do cromossomo X, em pacientes nuligrávidas apresentando amenorréia secundária e infertilidade. Nenhuma paciente referia história familiar de falência ovariana prematura e relatavam desenvolvimento puberal normal. A avaliação genética mostrou deleção distal no braço longo do cromossomo X, sendo os resultados 46,X,del(Xq22) e 46,X,del(Xq13q28), respectivamente. Após o diagnóstico as pacientes optaram por fertilização in vitro com óvulos doados.<br>Premature ovarian failure may be idiopathic or associated with several autoimmune and genetic disorders as X chromosome deletions. We report two cases of preamture ovarian failure associated with a deletion in the long arm of X chromosome. Both patients were nulligravidas presenting secondary amenorrhea and complaints of infertility, without family history of premature ovarian failure and reporting normal puberal development. Their karyotypes showed deletions of the distal long arm of all X chromosomes and were 46,X, del(Xq22) and 46,X, del(Xq13q28), respectively. After the diagnosis the patients decided to be submitted to an in vitro fertilization with egg donation

Injeção intracitoplasmática de espermatozóides na azoospermia não-obstrutiva: comparação com histopatologia testicular prévia Resultados de la inyección intracitoplasmática de espermatozoides en hombres con azoospermia no obstructiva: utilidad de la biopsia testicular previa Outcome of intracytoplasmic sperm injection in non-obstructive azoospermia according to previous testicular histology

Objetivo: avaliar o resultado de injeção intacitoplasmática de espermatozóides (ICSI) em homens com azoospermia não obstrutiva de acordo com a histologia testicular prévia. Desenho: estudo retrospectivo e transversal. Materiais e métodos: foram estudados os resultados laboratoriais e clínicos em 59 casais (79 ciclos) submetidos a ICSI com uso de espermatozoide testicular. Foram divididos três grupos de acordo com a histologia testicular obtida em biópsia a fertilização (hipoespermatogênese, parada de maturação espermática e aplasia de células germinativas) e os resultados da ICSI foram comparados entre os grupos. Resultados: o achado histoplatológico mais frequante foi hipoespermatogenese (61%), seguido por parada de maturação (22%) e aplasia de células germinativas (17%). A recuperação espermática e a taxa de fertilização oocitária foram superiores no grupo com hipoespermatogênese (p Objetivo: evaluar el resultado de la inyección intracitoplasmática de espermatozoides (ICSI) en parejas cuyos hombres mostraron azoospermia no obstructiva en conformidad con el hallazgo histológico del testículo. Diseño: estudio retrospectivo con análisis transversal. Materiales y métodos: han sido estudiados los resultados de laboratorio y clínicos en 59 parejas (79 ciclos) sometidas a la ICSI. Los hombres han sido divididos en 3 grupos de acuerdo con el reporte histológico obtenido en biopsia previa a la fertilización (hipoespermatogénesis, detención de la maduración espermática y aplasia de las células germinativas) y los resultados han sido comparados entre los grupos. Resultados: el hallazgo principal fue la hipoespermatogénesis (61%), seguido por la detención de la maduración espermática (22%) y la aplasia de las células germinativas (17%). Los espermatozoides estuvieron presentes en 87,7% y la tasa de fertilización (58,8%) en los casos de hipoespematogenesis fue significativamente más grande (p Objective: evaluating ICSI outcome using testicular spermatozoa in patients having non-obstructive azoospermia according to the histological finding of a previous testicular biopsy. Design: retrospective and transversal study. Patients and methods: we evaluated the laboratory outcome and clinical results of 59 couples undergoing 79 ICSI cycles with testicular sperm retrieval. These patients were divided into three groups according to testicular histology (hypospermatogenesis, maturation arrest and germ cell aplasia) revealed in biopsy prior to ICSI. The ICSI was compared to the other groups. Results : the most frequent testicular histological finding was hypospermatogenesis (61%), followed by maturation arrest (22%) and germ cell aplasia (17%). Sperm recovery and oocyte fertilisation were higher in the hypospermatogenesis group (p < 0,01) than in maturation arrest (50% and 40.7%) and germ cell aplasia (21.4% and 36.8%). Embryo cleavage was higher in patients having hypospermatogenesis (95.9%) followed by maturation arrest (87.5%) and germ cell aplasia (71.4%) (p = 0.001). The groups presented no difference in embryo development. Total clinical pregnancy rate per ICSI cycles and per cycles with embryo transfer were 25.3% and 37.7%, respectively. Conclusions: testicular biopsy has clinical value when counselling infertile couples. Although patients with hypospermatogenesis returned the best results, sperm recovery and oocyte fertilization are possible, even in cases where no spermatozoa were found in testicular biopsy

Septo uterino, duplicação cervical e septo vaginal: relato de rara malformação mülleriana com gestação a termo Septate uterus, cervical duplication and vaginal septum: a report of an uncommon malformation with normal term pregnancy

Apresentamos um caso de gestação espontânea em uma paciente com útero septado completo e duplicação cervical. Paciente com 34 anos, branca, nuligesta, ciclos regulares, com suspeita de septo uterino em exame ecográfico. Ao exame, apresentava septo vaginal longitudinal até a região himenal e dois colos uterinos. Solicitada ecografia pélvica tridimensional que evidenciou duplicação cervical, septo uterino do istmo à cavidade endometrial e ausência de divisão do corpo uterino, compatível com útero septado completo e duplicação cervical verdadeira. Um mês após, relatou relação sexual desprotegida e atraso menstrual. Ao exame ecográfico foi visualizado saco gestacional único na cavidade uterina direita. Apresentou gestação sem intercorrências. A cesariana ocorreu com 37 semanas, com recém-nascido do sexo feminino saudável e puerpério normal. Esse caso ilustra uma gestação espontânea, sem intercorrências, em uma rara anomalia, cujo impacto reprodutivo ainda não está totalmente elucidado.<br>This report describes an unusual case of spontaneous pregnancy in a patient with Müllerian anomaly. The patient was a 34-years old, white, nulligravida, with regular menstrual cycles, and suspected uterine septum observed during a routine ultrasonographic examination. The gynecological examination revealed a complete longitudinal vaginal septum and two uterine cervices. Three-dimensional pelvic ultrasonography showed cervix duplication, uterine septum from isthmus to endometrial cavity and absence of uterine body division, compatible with complete uterine septum and true dual cervices. She returned after one month and reported unprotected sexual intercourse and delayed menstrual period. She was pregnant, had a good pregnancy evolution, and delivered a healthy term baby girl, by cesarean section, at 37 weeks of pregnancy. This report describes a case of normal-term pregnancy in a patient with a rare anomaly (vaginal septum and two cervices) who became spontaneously pregnant without treatment

Septo uterino, duplicação cervical e septo vaginal: relato de uma malformação incomum Utero septado, duplicación del cuello y septo vaginal: informe de una rara malformación Septate uterus, cervical duplication and vaginal septum: a report of an uncommon malformation

Objetivo: describir una rara alteración de la fusión de los canales de Müller. Diseño: presentación de caso Reporte del caso: una paciente asiste a la consulta con un examen de ultrasonido en cuya descripción se plantea la sospecha de útero septado. El examen ginecológico reveló un septo vaginal longitudinal, que llegaba hasta la región del himen y la presencia de dos cuellos. La ecografía pélvica tridimensional mostró duplicación del cuello, útero septado que comprometía desde el istmo hasta la cavidad uterina pero sin división del cuerpo uterino, compatible con útero septado y cuello doble. Conclusión: este caso representa una rara malformación no incluida dentro de la clasificación habitual de las malformaciones Müllerianas y que no tiene explicación embriogénica, que se apoya en la teoría de la fusión unidireccional de los canales de Müller. La ecografía tridimensional, es un examen simple y de bajo costo y demostró ser una buena opción para el diagnóstico definitivo de esta malformación, por lo que debe ser considerada dentro del arsenal de exámenes complementarios.Objective: to describe a case of an unusual müllerian anomaly. Design: case report. Case report: a 34 years old white nulligravida presented with complains of suspected uterine septum observed during a routine ultrasonographic examination. Gynecological examination revealed a longitudinal vaginal septum which arrived in hymeneal region and two uterine cervixes. Three dimensional pelvic ultrasonography showed cervix duplication, uterine septum from isthmus to endometrial cavity and absence of uterine body division, compatible with complete uterine septum and true dual cervices. Conclusion: this case represents a rare malformation that is not included in usual classification of müllerian malformations and is not explained by the traditional embryologic vision that supports the unidirectional müllerian fusion. The three-dimensional ultrasonography, a non-invasive and lower cost exam, is a diagnostic option that must be considered in diagnosis arsenal of müllerian malformations

Efficacy and tolerance of metronidazole and miconazole nitrate in treatment of vaginitis

Objective: To evaluate the efficacy and tolerability of a vaginal pessary containing 750 mg of metronidazole and 200 mg of miconazole nitrate used daily for 7 days in the treatment of vaginitis. Methods: Ninety-two women with vaginitis participated in this phase 3 study using one vaginal pessary daily for 7 days. Gynecological and microbiological evaluations were carried out prior to and following treatment. Results: Reductions occurred in symptoms and signs of vaginitis. Clinical cure rate was 87.7%, while the cure rates according to microscopy and Candida albicans culture were 81.8% and 73.9%, respectively. The cure rate for bacterial vaginosis was 75% and culture of Gardnerella vaginalis turned negative in 63.6% of cases following treatment. The medication was well tolerated. Conclusion: Use of a combination of 750 mg of metronidazole and 200 mg of miconazole in a single daily application was found to be effective in the treatment of the most common causes of vaginitis. (c) 2008 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved

Atelosteogenesis Type 2/Diastrophic Dysplasia Phenotypic Spectrum: From Prenatal to Preimplantation Genetic Diagnosis

Atelosteogenesis type II (AO2) and diastrophic dysplasia (DTD) are two recessively inherited, severe skeletal dysplasias caused by mutations in the SLC26A2 gene. AO2 is an invariably lethal condition, while DTD patients may reach adult life, although both diseases have overlapping diagnostic features. Here we report a patient with an intermediate phenotype between AO2 and DTD and present the successful application of preimplantation genetic diagnosis (PGD) in this situation. Sequencing of SLC26A2 alleles in the infant identified two compound heterozygous mutations, p.Arg178Ter and p.Arg279Trp, of paternal and maternal origin, respectively. At request from the parents, PGD was developed by haplotype mapping of parental SLC26A2 alleles in eleven five-day embryos. Transference to the mother was attempted twice, finally resulting in pregnancy and delivery of a healthy baby. This exemplifies the utility of PGD for inherited lethal conditions with a significant risk of recurrence, and highlights the importance of accurate diagnosis of skeletal dysplasias with prenatal manifestation

Atelosteogenesis Type 2/Diastrophic Dysplasia Phenotypic Spectrum: From Prenatal to Preimplantation Genetic Diagnosis

Atelosteogenesis type II (AO2) and diastrophic dysplasia (DTD) are two recessively inherited, severe skeletal dysplasias caused by mutations in the SLC26A2 gene. AO2 is an invariably lethal condition, while DTD patients may reach adult life, although both diseases have overlapping diagnostic features. Here we report a patient with an intermediate phenotype between AO2 and DTD and present the successful application of preimplantation genetic diagnosis (PGD) in this situation. Sequencing of SLC26A2 alleles in the infant identified two compound heterozygous mutations, p.Arg178Ter and p.Arg279Trp, of paternal and maternal origin, respectively. At request from the parents, PGD was developed by haplotype mapping of parental SLC26A2 alleles in eleven five-day embryos. Transference to the mother was attempted twice, finally resulting in pregnancy and delivery of a healthy baby. This exemplifies the utility of PGD for inherited lethal conditions with a significant risk of recurrence, and highlights the importance of accurate diagnosis of skeletal dysplasias with prenatal manifestation