Preservação da fertilidade masculina no Centro Hospitalar de Vila Nova de Gaia/Espinho EPE - 17 anos de experiência / Preserving male fertility at the Centro Hospitalar de Vila Nova de Gaia/Espinho EPE -17 years of experience

Objetivo. Reportar a nossa experiência nos últimos 17 anos na preservação da fertilidade masculina por doença oncológica, genética, imunológica e endocrinológica, assim como por alterações graves da espermatogénese. Material e métodos. avaliação de parâmetros demográficos, características do esperma e resultados obtidos com amostras descongeladas em ciclos de procriação medicamente assistida (PMA). Resultados. Duzentos e setenta e um homens com uma idade média de 31,5±6,3 anos (16‐52 anos) foram referenciados para PF. A doença oncológica foi a causa mais comum (34,3%), seguida de azoospermia secretora ou não obstrutiva, oligoastenoteratozoospermia (TAO) grave, doença genética, hipogonadismo/atrofia testicular, doença auto‐imune, doença endócrino‐metabólica e pré‐cirurgia potencialmente comprometedora da fertilidade. Dentro da doença oncológica, o tumor do testículo foi a neoplasia mais comum (64,5%), seguido do cancro hematológico e de etiologias variadas. Na doença genética, a síndrome de Klinefelter foi a condição mais frequente (50%). No total 194 homens ficaram com amostras criopreservadas (1.099 amostras no total; 5,7±3,4 por paciente). Os homens com doença oncológica tiveram, em média, um número significativo superior de amostras congeladas (p<0,001). Os casos de tumor do testículo apresentaram uma concentração média de espermatozoides/ml significativamente inferior face aos outros tumores (p<0,005). Durante estes 17 anos, 58 homens (29,9%) procuraram o centro para realização de técnicas de PMA com amostras descongeladas. Foram realizados 87 ciclos, com 19 gestações (21,8%). Nasceram 15 recém‐nascidos (RN) saudáveis. Conclusões. Ainda que o número de homens que tenham procurado o uso das amostras armazenadas, não se pode desvalorizar o impacto psicológico positivo da PF, tendo em conta que pode ser a única possibilidade de paternidade biológica (AU)

Objective. A report is presented of 17 years of experience in male fertility preservation due to oncological, genetic, immunological and endocrinological disease, as well as severe spermatogenesis alterations. Material and methods. An evaluation is made of demographic parameters, sperm characteristics and results of assisted reproduction techniques cycles with thawed samples. Results. A total of 271 men with a mean age 31.5±6.3 years (16 to 52 years) were referred to sperm banking. The most common cause was oncological disease (34.3%), followed by secretory azoospermia, oligoasthenoteratozoospermia, genetic disease, testicular atrophy/hypogonadism, auto‐immune disease, endocrine‐metabolic disease, and prior to potentially fertility damage surgery. Among oncological disease, testicular tumour was the most common cancer (64.5%), followed by haematological cancer, and other aetiologies. Klinefelter syndrome was the most common (50%) among the genetic diseases. A total of 194 men had samples cryopreserved (1099 total samples; 5.7±3.4 per patient). Men with oncological disease had a significantly higher number of cryopreserved samples (p<.001). Testicular tumour cases had a mean lower sperm concentration relative to other tumours (p<.005). During these 17 years, 58 men (29.9%) asked to have assisted reproduction techniques performed with their thawed samples. The 87 cycles performed resulted in 19 pregnancies (21.8%) and 15 healthy newborns. Conclusions. Although the number of men asking to use their cryopreserved samples is low, we cannot undervalue the positive psychological impact of fertility preservation, taking in consideration that it can be the only possibility to biological fatherhood (AU)

Trombofilia e terapêutica com heparina de baixo peso molecular na falha de implantação / Thrombophilia and therapy with low-molecular-weight heparin in implantation failure

Introdução: Estudos recentes demonstraram a associação de trombofilias e com falha de implantação. O objectivo deste trabalho foi avaliar o impacto na taxa de gravidez da pesquisa de trombofilias e terapêutica com heparina de baixo peso molecular (HBPM) nas mulheres em que se verifique falha de implantação. Material E Métodos: Estudo retrospectivo observacional controlado de todos os casos de falha de implantação durante 3 anos. Foram constituídos 2 grupos: grupo A, em que foi efectuada pesquisa de trombofilias, tendo sido instituída terapêutica com HBPM nos casos alterados, a partir da data da punção folicular; grupo B, em que não foi efectuada pesquisa de trombofilias nem terapêutica com HBPM. Foi realizada a comparação da taxa de implantação, taxa de gravidez e taxa de nados vivos entre ambos os grupos. Resultados: Foram incluídos 33 casos no grupo A e 24 casos no grupo B. O resultado da pesquisa de trombofilias, efectuada apenas no grupo A, foi alterada em todos os casos, com presença de mutação para o gene da MTHFR em 87,88 % dos casos e mutações do gene do PAI-1 em 75,76 % dos casos. Verificou- se um aumento estatisticamente significativo da taxa de implantação e da taxa de gravidez no grupo A (29,09 % vs 10,26 %, p <0,05, e 45, 45 % vs 12,50 %, p <0,05). A taxa de abortamento foi sobreponível em ambos os grupos. A terapêutica com HBPM associou-se a um aumento significativo da taxa de nados vivos por transferência (36,36 % vs 12,50 % respectivamente no grupo A e B, p <0,05). Não se verificaram complicações associadas à terapêutica anticoagulante. Conclusão: As trombofilias parecem representar um importante papel no sucesso/insucesso da implantação embrionária. A terapêutica com HBPM nas mulheres com trombofilia associou-se a um aumento significativo da taxa de implantação, da taxa de gravidez e da taxa de nados vivos (AU)

Introduction: Recent studies have reported an association between thrombophilia and implantation failure. The aim of this study was to evaluate the impact on the pregnancy rate of thrombophilia research and therapy with low-molecularweight heparin (LMWH) in women with implantation failure. Material and Methods: Retrospective observational controlled study of all cases of implantation failure during 3 years. Cases were divided into two groups: Group A, where thrombophilic defects were searched, and therapy with LMWH was started in altered cases, from the date of ovary punction; Group B, in which thrombophilia research wasn’t performed nor anticoagulant therapy was started. Primary outcomes were the implantation, pregnancy and live birth rates. Results: There were 33 patients included in group A and 24 patients in group B. The search for thrombophilia, performed only in group A, was altered in all cases, with the presence of mutations in the MTHFR gene in 87.88 % of cases and PAI- 1 gene mutations in 75.76 % of cases. There was a statistically significant increase in the implantation and pregnancy rates in group A (29.10 % vs. 10.26 %, p <0.05, and 45.45 % vs. 12.50 %, p <0.05). The abortion rate was similar in both groups. LMWH therapy was associated with a significant increase in live birth rate per transfer (36.36 % vs. 12.50 % in group A and B respectively, p <0.05). There were no complications associated with anticoagulant therapy. Conclusion: Thrombophilia seems to play an important role in the success/failure of embryo implantation. LMWH therapy in women with thrombophilia is associated with a significantly increased in implantation, pregnancy and live birth rates (AU)

Ultraestrutura de um caso de astenozoospermia / Ultrastructure of a case of asthenozoospermia

The article reports the case of a 40-year old man with no history of significant illness. The semen analysis identified total asthenozoospermia. Ultrastructural analysis by electron microscopy showed multiple mitochondrial sheath and flagellum structure anomalies (incomplete/disorganized axoneme, absence of outer dense fibers and fibrous sheath) that explain the sperm immotility. As far as we know, the causes have still not been determined and the possibilities of reproduction involve the use of ICSI with low probability of success (AU)

O artigo apresenta o caso de um paciente de 40 anos sem antecendentes de doenças significativas conhecidas. No espermograma identificou-se astenozoospermia total. Na análise ultraestrutural por microscopia eletrónica de transmissão observaram-se múltiplas nomalias na baínha mitocondrial e na estrutural do flagelo (axonemas incompletos/desorganizados, ausência de fibras densas externas e segmentos de baínha fibrosa) explicativos da imobilidade espermática. As causas da patologia são desconhecidas à luz da ciência atual e as possibilidades de reprodução implicam o recurso à ICSI com baixa probabilidade de sucesso (AU)

Outcomes from ovarian hyperstimulation following the sole administration of gonadotrophin-releasing hormone agonist in the context of in vitro fertilization: report of two cases and review of the literature.

OBJECTIVE: To report the outcomes from two cases of ovarian stimulation following the sole administration of gonadotrophin-releasing hormone agonist (GnRHa) in the context of in vitro fertilization (IVF). DESIGN: A case study was conducted. SETTING: National Referral Unit of Reproductive Medicine. PATIENTS: Two infertile women undergoing IVF participated in the study. INTERVENTIONS: Controlled ovarian hyperstimulation using a long protocol. GnRHa (Buserelin) was started in the luteal phase, in a dose of 600 µg/day, for 12 days. MAIN OUTCOME MEASURES: Number of retrieved oocytes, fertilization rate, number of embryos transferred, implantation rate, ongoing pregnancy, and live birth. RESULTS: Both women underwent egg retrieval and transfer of good quality embryos. One of them conceived and recently gave birth to a healthy full-term baby. CONCLUSIONS: The ovarian hyperstimulation after the sole administration of GnRHa is a rare condition. Oocyte retrieval may be a reasonable treatment under these circumstances instead of cycle cancellation. As far as it is known, this is the third case reported of a live birth following the sole administration of GnRHa in the context of IVF.

Estimulação ovariana controlada e inseminação intrauterina: uma terapia atual? / Controlled ovarian stimulation and intrauterine insemination: an actual therapy?

OBJETIVO: Analisar a taxa de gravidez na inseminação intrauterina (IIU), aferindo eventuais fatores prognósticos de sucesso. MÉTODOS: Estudo retrospectivo de ciclos de IIU ocorridos de janeiro de 2007 a julho de 2010 em uma Unidade de Medicina da Reprodução do Hospital Vila Nova de Gaia. Os ciclos foram precedidos por estimulação ovárica controlada e monitorizada por ecografia endovaginal. Avaliou-se a taxa de gravidez em função da idade da mulher, tipo e duração da infertilidade, motilidade no espermograma, número de folículos e fármaco usado na estimulação ovárica. A análise estatística foi efetuada com o Statistical Package for the Social Sciences (SPSS 17), com um nível de significância 5 por cento (p<0,05). RESULTADOS: O estudo integrou 139 casais submetidos a 220 ciclos de IIU. A taxa global de gravidez por ciclo foi de 18,6 por cento e, das 41 grávidas, 5 foram gemelares (12,1 por cento). Ocorreu maior taxa de gravidez abaixo dos 30 anos (28,5 vs 15,7 por cento; p=0,02), duração de infertilidade <3 anos (23,8 vs 13,9 por cento; p=0.05), espermograma sem alterações da motilidade (23,2 vs 10,3 por cento; p=0,01) e na presença de dois folículos no momento da ovulação face ao desenvolvimento monofolicular (27,7 vs 14,2 por cento; p=0,030). As taxas gravídicas com citrato de clomifeno, gonadotrofinas e a sua associação foram de 13,0, 26,1 e 28,6 por cento, respectivamente, com diferença significativa na taxa de gravidez clínica entre citrato de clomifeno e gonadotrofinas. CONCLUSÕES: A IIU mantém-se como um natural ponto de partida para casais convenientemente selecionados. Idades mais jovens, menor duração da infertilidade e espermograma sem alterações na motilidade constituem fatores de bom prognóstico e a estimulação com gonadotrofinas contribui para melhoria da taxa de gravidez.

PURPOSE: To evaluate the pregnancy rate in intrauterine insemination (IUI), and to determine possible prognostic factors of successful pregnancy. METHODS: A retrospective study of IUI cycles performed in the Reproductive Medicine Unit of Vila Nova de Gaia Hospital, between January 2007 and July 2010. The IUI cycles were preceded by ovarian stimulation and monitored by vaginal ultrasound. Clinical pregnancy rates were analyzed according to the woman’s age, type and duration of infertility, spermatozoa parameters assessed in the spermogram, number of mature follicles and the drug used for ovarian stimulation. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS17), with the level of significance set at p<0.05. RESULTS: The study comprised 139 couples who underwent 220 IUI cycles. The absolute pregnancy rate per cycle was 18.6 percent. Of the 41 clinical pregnancies, 5 were twin pregnancies (12.1 percent). The pregnancy rate was higher at ages <30 years (28.5 vs 15.7 percent; p=0.024), duration of infertility <3 years (23.8 vs 13.9 percent; p=0.05), normal sperm motility (23.2 vs 10.3 percent; p=0.01) and with two follicles at the time of insemination (27.7 vs 14.2 percent for monofollicular growth; p=0.030). The pregnancy rates obtained with clomiphene citrate, gonadotropins and combined clomiphene citrate/gonadotropin were 13.0, 26.1 and 28.6 percent, respectively, with a statistically significant difference in clinical pregnancy rate between clomiphene citrate and gonadotropin. CONCLUSIONS: IUI remains a natural starting point for conveniently selected couples with infertility. Younger age and normal sperm motility are good prognostic factors. Gonadotrophin stimulation seems to be an important tool for improving the pregnancy rate of IUI.

[Controlled ovarian stimulation and intrauterine insemination: an actual therapy?]. / Estimulação ovariana controlada e inseminação intrauterina: uma terapia atual?

PURPOSE: To evaluate the pregnancy rate in intrauterine insemination (IUI), and to determine possible prognostic factors of successful pregnancy. METHODS: A retrospective study of IUI cycles performed in the Reproductive Medicine Unit of Vila Nova de Gaia Hospital, between January 2007 and July 2010. The IUI cycles were preceded by ovarian stimulation and monitored by vaginal ultrasound. Clinical pregnancy rates were analyzed according to the woman's age, type and duration of infertility, spermatozoa parameters assessed in the spermogram, number of mature follicles and the drug used for ovarian stimulation. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS17), with the level of significance set at p<0.05. RESULTS: The study comprised 139 couples who underwent 220 IUI cycles. The absolute pregnancy rate per cycle was 18.6%. Of the 41 clinical pregnancies, 5 were twin pregnancies (12.1%). The pregnancy rate was higher at ages <30 years (28.5 vs 15.7%; p=0.024), duration of infertility <3 years (23.8 vs 13.9%; p=0.05), normal sperm motility (23.2 vs 10.3%; p=0.01) and with two follicles at the time of insemination (27.7 vs 14.2% for monofollicular growth; p=0.030). The pregnancy rates obtained with clomiphene citrate, gonadotropins and combined clomiphene citrate/gonadotropin were 13.0, 26.1 and 28.6%, respectively, with a statistically significant difference in clinical pregnancy rate between clomiphene citrate and gonadotropin. CONCLUSIONS: IUI remains a natural starting point for conveniently selected couples with infertility. Younger age and normal sperm motility are good prognostic factors. Gonadotrophin stimulation seems to be an important tool for improving the pregnancy rate of IUI.