HCG、FSH联合治疗低促性腺激素性性腺功能减退症29例报告

目的 探讨人绒毛膜促性腺激素(HCG)和促卵泡激素(FSH)联合治疗男性低促性腺激素性性腺功能减退症的有效性和安全性.方法 29例男性低促性腺激素性性腺功能减退症23例,Kallmann综合征6例.治疗方案:采用联合HCG 2000 IU,2次/周;FSH 75 IU,3次/周,肌肉注射,连续用药至少3个月. 结果治疗后所有患者体力改善,体质增强;22例患者出现胡须、阴毛和(或)腋毛.睾丸体积治疗前(2.68±1.44)ml,治疗后(8.93±3.24)ml(P<0.01);促卵泡激素(FSH)、促黄体激素(LH)和睾酮(T)水平有所提高(P<0.05);12例患者出现遗精现象,8例有精子生成.结论 对男性低促性腺激素性性腺功能减退症,用HCG和FSH治疗能促进青春期第二性征发育,并可使部分睾丸恢复产生雄激素和生成精子功能.     

HCG and HMG treatment of male infertility with pituitary problems

A case is presented of a twenty-nine-year-old acromegalic man with sexual problems and fertility disturbance due to pituitary adenoma, who successfully fathered. Various endocrinologic studies, skill x-ray film, and computerized tomography (CT) scan revealed a pituitary adenoma. Testicular biopsy specimen also supported that the cause of sexual problems and fertility disturbance was secondary in origin. One month after transsphenoidal pituitary adenectomy, administration of human chorionic gonadotropin and human menopausal gonadotropin was started. His potency was improved immediately after start of the treatment, and his wife became pregnant five months later.     

Pregnancy after intracytoplasmic sperm injection following extended sperm preparation and hormone therapy in an azoospermic man with maturation arrest and microlithiasis: a case report and literature review

In the management of azoospermia, a combination of testicular sperm extraction and intracytoplasmic sperm injection (ICSI) is usually the most successful option for fatherhood. However, an outstanding question remains: How can at least a few spermatozoa be obtained from the ejaculate, thus avoiding the need for a surgical procedure? A 36‐year‐old man presented to Assisted Reproduction Unit with his 26‐year‐old wife. The ultrasound assessment revealed bilateral microlithiasis. Two spermograms revealed absolute azoospermia. Levels of follicle‐stimulating hormone (FSH) and luteinising hormone were normal–low. The patient underwent 10 months of treatment with clomiphene citrate. A bilateral testicular sperm extraction failed to retrieve spermatozoa and revealed a maturation arrest at spermatocyte/spermatid stages depending on the tubules. Clomiphene citrate was replaced with recombinant FSH (rFSH). After 9‐month treatment with rFSH, motile spermatozoa from droplets of ejaculate pellet were cryopreserved as a single straw. Ovarian stimulation was provided using classic antagonist protocol, and five mature oocytes were collected. Two consecutive fresh semen samples on the day of ICSI yielded seven motile spermatozoa, and fertilisation was achieved in all five oocytes. On day 3, two embryos were transferred, yielding positive beta‐human chorionic gonadotropin and a healthy delivery of a boy and a girl.     

Outcome of gonadotropin therapy for male hypogonadotropic hypogonadism at university affiliated male infertility centers: a 30-year retrospective study

PURPOSE: Hypogonadotropic hypogonadism (HH) is an uncommon cause of male infertility. Even specialized centers see small numbers of patients and have little experience in restoring fertility in these patients. To explore the phenotypic heterogeneity and treatment outcome of HH, we summarized our 30-year experience. MATERIALS AND METHODS: Medical charts of 36 male patients (age range 11 to 42 years) with HH (81% primary, 19% secondary) treated at university affiliated male infertility centers were reviewed. Pubic hair stage, genital stage, testicular volume (TV), sexual function and sperm production were determined before and after human chorionic gonadotropin/human menopausal gonadotropin (hCG/hMG) treatment. Differences were analyzed statistically. RESULTS: The population was stratified according to initial TV into a small testis subset (TV less than 4 ml in 23) and a large testis subset (TV 4 ml or greater in 13). Comparison of these 2 subsets revealed significant differences in the incidence of cryptorchidism (39% vs 8%) and Kallmann's syndrome (22% vs 0%), pubic hair stage (1.3 +/- 0.5 vs 3.5 +/- 1.4), genital stage (1.2 +/- 0.4 vs 3.9 +/- 0.9) and TV (1.6 +/- 0.9 vs 7.5 +/- 3.5 ml). Long-term administration of hCG/hMG for 12 to 240 months (average 56 +/- 11) resulted in sperm production in only 36% of the small testis subjects but in 71% of the large testis subjects. CONCLUSIONS: Initial TV values provide insight into phenotypic variables such as time of onset and severity in patients with primary or secondary HH, and may predict sperm output in response to hCG/hMG therapy.     

Fertilisation failure after intracytoplasmic sperm injection is not associated with sperm aneuploidy of a globozoospermic patient

The objective of this study was to determine the aneuploidy rate in spermatozoa from a globozoospermic patient who underwent three unsuccessful intracytoplasmic sperm injection (ICSI) treatment cycles together with his wife. The aneuploidy rates of chromosomes 13, 18, 21, X and Y as well as the diploidy rate in the spermatozoa of this man were evaluated by fluorescence in situ hybridisation to clarify if chromosomal aneuploidy could be a cause for the low fertilisation rate observed in this case. In the spermatozoa of our patient no increase in aneuploidy rates was found for the tested chromosomes (0.0% disomies of chromosomes 13, 18 and 21 with a diploidy rate of 0.6%; X/Y missegregation: 0.6%) indicating that the ICSI outcome of the couple was not impaired by sperm aneuploidy of the globozoospermic man.     

Treatment of infertility due to anejaculation in the male with electroejaculation and intracytoplasmic sperm injection

PURPOSE: We tested the hypothesis that spinal cord injury and/or anejaculation affects the outcome of intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: From November 1993 to October 1998 we obtained and prospectively reviewed data on 34 ICSI cycles using electroejaculated sperm, 620 male factor infertility ICSI cycles using normal ejaculated sperm and 120 cases of obstructive azoospermia, in which microsurgical epididymal aspiration and testicular sperm extraction-ICSI were done in 93 and 27, respectively. RESULTS: A total of 34 ICSI cycles were performed in 17 couples with male infertility due to anejaculation secondary to spinal cord injury in 10 patients and retroperitoneal lymph node dissection in 5, and idiopathic in 2. In all 17 couples at least 3 previous intrauterine insemination cycles had failed. After electroejaculation 11 men had oligozoospermia and 6 normal sperm density. Median sperm retrieval volume plus or minus standard deviation was 1.9 +/- 1.9 ml., median sperm concentration 70.7 +/- 60.2 x 106 sperm per ml., median motility 10.7% +/- 10.8% and median forward progression 2.3 +/- 0.5 (scale 1 to 4). In the anejaculation group ICSI resulted in a median fertilization of 60% +/- 28%, 15% pregnancies per cycle and 29% pregnancies per couple. In the control group of 620 ICSI cycles from ejaculated specimens obtained from male patients with infertility median fertilization was 58% +/- 26%, and there were 39% pregnancies per cycle and 47% pregnancies per couple. The rate of pregnancies per embryo transfer and per couple was higher in the control than in the electroejaculation-ICSI group (p <0.05). However, there was no statistically significant difference in the fertilization rate. CONCLUSIONS: ICSI or in vitro fertilization is a viable alternative for patients with anejaculation in whom intrauterine insemination failed. While the fertilization rate is similar in these couples, the pregnancy rate is significantly lower than that achieved with ejaculated specimens from patients with severe male factor infertility. ICSI is a viable alternative for a patient with anejaculation in whom intrauterine insemination or in vitro fertilization failed.     

Pregnancy following intracytoplasmic sperm injection of immotile spermatozoa selected by the hypo-osmotic swelling-test: a case report

Summary.  The success of intracytoplasmic sperm injection (ICSI) is poor when only immotile spermatozoa can be retrieved. In a couple with complete male asthenozoospermia the possible use of the hypo-osmotic swelling test to select spermatozoa for microinjection was examined. Following incubation in hypo-osmotic medium (Hypo 10, IVF Science, Göteborg, Sweden), 26% of immotile spermatozoa showed signs of sperm swelling (HOS-positive). After injection of HOS-positive spermatozoa, 5 out of 12 oocytes fertilized (41%) and after transfer of three embryos a healthy singleton pregnancy was achieved. In a previous ICSI cycle of this couple without preselection of spermatozoa by the HOS test, only 1 out of 10 oocytes fertilized. It is concluded that selection of spermatozoa by hypo-osmotic swelling-test prior to sperm microinjection seems to be a valuable tool to increase the fertilization rate in cases with complete asthenozoospermia.     

ICSI完全受精失败的机制、原因及处理

卵胞浆内单精子注射(ICSI)已广泛用于治疗男性因素不育,但ICSI后完全受精失败(total fertilization failure,TFF)的发生率仍有1%～4%。卵子激活失败(oocyte activation failure,OAF)是ICSI-TTF的主要机制。本文综述了卵母细胞激活的机制、ICSI-TTF的发生机制和原因、OAF的鉴别方法以及相应的处理策略。     

Recovery of ejaculated spermatozoa for intracytoplasmic sperm injection after anti-inflammatory treatment of an azoospermic patient with genital tract infection: a case report

In this paper our experiences with anti-inflammatory treatment of an infertile patient with azoospermia and concomitant silent genital infection are reported. The patient was referred to our fertility centre with prediagnosed non-obstructive azoospermia and no spermatozoa were found in the ejaculate on two occasions. The patient showed leukocytospermia and was suspected to be affected by genital infection. Therefore, anti-inflammatory treatment was initiated and 8 weeks later examination of the ejaculate revealed a decreased number of leukocytes and the presence of few but motile spermatozoa. Subsequently, two ICSI cycles were performed with anti-inflammatory therapy in parallel and a sufficient number of spermatozoa could be retrieved for injection. However, in a third cycle without previous treatment, examination of the ejaculate again revealed azoospermia and leukocytospermia. It is concluded that, in cases of azoospermia and chronic genital infection, some patients will benefit from anti-inflammatory treatment prior to and during ICSI treatment. This may allow retrieval of spermatozoa from the ejaculate and thus may avoid the need for a therapeutic testicular biopsy. Using this approach, sufficient spermatozoa in three out of four ICSI cycles could be retrieved and a pregnancy was finally achieved.     

High level of intracellular sperm oxidative stress negatively influences embryo pronuclear formation after intracytoplasmic sperm injection treatment

This study evaluates the relationship between sperm intracellular reactive oxygen species (ROS; H₂O₂, O₂), DNA fragmentation (DF), low mitochondria membrane potential (MMP) of sperm and normal pronuclear formation among intracytoplasmic sperm injection (ICSI) patients. Semen samples were obtained from 62 infertile male who were candidates for ICSI treatment. After sperm processing, metaphase II (MII) oocytes were injected, and the mean percentages of intracellular ROS, MMP and DF were evaluated using flow cytometry. The mean percentages of pronuclear formation and zygote score (Z) were also recorded, and Pearson, Spearman's rank correlation coefficient and Kruskal–Wallis tests were applied to analyse the data. The amounts of sperm intracellular H₂O₂ and ˙ had significant positive correlation with low MMP (P < 0.01). The intracellular ROS had a negative correlation with pronuclear formation (P < 0.05), and its effect was higher than 66.66%. In addition, the mean percentages of neither H₂O₂ nor ˙ affected the quality of pronuclear embryos (Z‐score). This study shows that although high levels of both sperm intracellular H₂O₂ and ˙ in ICSI patients have deleterious effect on sperm MMP, only H₂O₂ may interfere in pronuclear formation.     

Prognostic value of male diagnostic profiles in intracytoplasmic sperm injection (ICSI)

Possible correlations between male hormone and semen parameters with pregnancy and oocyte fertilization rates following intracytoplasmic sperm injection (ICSI) were investigated. The study is based on 290 couples who underwent ICSI therapy for the first time. The parameters evaluated were male age, serum levels of follicle stimulating hormone (FSH) and testosterone, sperm concentration, sperm motility, normal sperm morphology, index of teratozoospermia (TZI) and sperm vitality. A marginal, barely significant association was found between the fertilization rate and serum FSH levels in the male partner ( p =  0.046). There was no relevant association between male parameters and pregnancy rates. The study confirms that male hormonal and semen parameters are of low prognostic value for the outcome of ICSI.     

Intracytoplasmic sperm injection as a complement to gonadotrophin treatment in infertile men with hypogonadotrophic hypogonadism

In this study we sought to determine whether intracytoplasmic sperm injection (ICSI) could improve the efficacy of treatment with gonadotrophins in gonadotrophin-deficient men in terms of pregnancy. A series of six adult men (aged 26-47 years) with hypogonadotrophic hypogonadism (HH) is reported: four men with prepubertal isolated idiopathic HH (IIHH) and two adult-onset HH, as part of hypopituitarism secondary to surgical treatment of a pituitary tumour. All were azoospermic. To restore spermatogenesis, all received hormonal treatment with intramuscular human menopausal gonadotrophins (HMG) and human chorionic gonadotrophin (HCG) for 2 to 23 months. High basal serum inhibin B was predictive of rapid and complete recovery of spermatogenesis. In the two adult-onset HH, a natural pregnancy was achieved within 3 months. The four men with IIHH underwent ICSI because of poor sperm quality. ICSI using fresh or frozen-thawed ejaculated spermatozoa was performed after 6-23 months of gonadotrophin treatment. ICSI provided good clinical results in terms of fertilization and embryo quality, and resulted in three pregnancies that ended in three term deliveries. In men with oligozoospermia related to prepubertal IIHH, ICSI shortens the hormonal treatment and enhances the chances of pregnancy.     

The influence of male age on treatment outcomes and neonatal birthweight following assisted reproduction technology involving intracytoplasmic sperm injection (ICSI) cycles

The aim of this study was to investigate the effect of male age on treatment outcomes and neonatal birthweight following intracytoplasmic sperm injection (ICSI). This study included 2,474 ICSI cycles. Male partners were stratified into 5‐year age categories (up to 25, 26–30, 31–35, 36–40 and 41 and up). Multilevel logistic regression was used to evaluate the relationship between male age and treatment outcomes. After adjusting for confounders, we found no difference in the clinical pregnancy rate. However, we observed that the 31‐ to 35‐year group had a higher odds of live birth than that of the >41‐year group (aOR 1.63, p = .03), and that the risk of abortion in the 31‐ to 35‐year group was lower than that of the reference group (aOR 0.41, p = .02). A total of 754 single‐foetus newborns and 556 twin newborns were analysed. Among the singletons, none of the variables differed among the five groups (p > .05). Among the twins, the infants in the 36‐ to 40‐year group had a lower neonatal birthweight and a higher low‐birthweight rate than those of the other groups (p < .05). Our study indicates that increased paternal age negatively affects the live birth and miscarriage rates. In addition, advanced paternal age may affect the birthweight of twins.     

Birth after intracytoplasmic sperm injection of ejaculated spermatozoa from a man with mosaic Klinefelter＇s syndrome

Aim: To report a birth after intracytoplasmic sperm injection (ICSI) of ejaculated spermatozoa from a man with mosaic Klinefelter‘s syndrome detected by fluorescence in situ hybridization (FISH) analysis. Methods: A 35-year-old man with a normal appearance consulted our hospital because of sterility over a 5-year period. Chromosome analysis showed low-incidence mosaic Klinefelter‘s syndrome. Using FISH, 96% hyperploidy of the lymphocytes was found. We examined the sex chromosome of the ejaculated spermatozoa. Using FISH, we examined 200 ejaculated spermatozoa and no hyperploidy was found. Results: The 33-year-old female partner of the male patient underwent an uncomplicated controlled ovarian hyperstimulation sequence using a combined recombinant-follicle stimulating hormone (rec-FSH) human menopausal gonadotrophin (hMG) protocol, following late luteal phase pituitary down regulation. This culminated in the retrieval of seven oocytes, six of which were fertilized with ICSI.One ICSI attempt led to clinical pregnancy with a healthy baby girl. Conclusion: We report a male patient with lowincidence mosaic Klinefelter‘s syndrome whose ejaculated spermatozoa were identified as being haploid by FISH before ICSI, leading to the successful pregnancy of his wife and the birth of a healthy baby girl.     

Influence of motility and vitality in intracytoplasmic sperm injection with ejaculated and testicular sperm

The vitality of spermatozoa used for intracytoplasmic sperm injection (ICSI) is a crucial factor for fertilization, establishment and outcome of a pregnancy in assisted reproductive technique cycles. The sperm origin may also be a limiting factor, although little is known about this issue. It is known that the motility of injected spermatozoa and their origin from ejaculate or testicular biopsies are important predictors in terms of fertilization, pregnancy and birth rates. Oocytes of patients in 2593 cycles were retrieved in our in vitro fertilization programme and inseminated via ICSI. We used motile (group 1, n = 2317) or immotile ejaculated spermatozoa (group 2, n = 79), motile sperm retrieved from testicular biopsies (group 3, n = 62) and immotile spermatozoa from testicular biopsies (group 4, n = 135). Female age and number of oocytes retrieved did not differ significantly among the groups. The fertilization rates were as follows: 67.1% in group 1, 49.8% in group 2, 68.3% in group 3 and 47.8% in group 4. The pregnancy rates in cases where three embryos had been transferred amounted to 35.7% in group 1, 17.3% in group 2, 38.3% in group 3 and 20.5% in group 4. The embryo quality showed no differences between groups 1 and 3 (14.5), and between groups 2 (11.8) and 4 (10.8). The abortion rate was similar in groups 1-3, but increased in group 4 (26.6%, 27.3%, 31.6% and 55.5%). Irrespective of their origin, the fertilization potential of injected spermatozoa was found to be influenced by motility. The resulting pregnancy and birth rates, i.e. the potential of the resulting embryos to implant and to achieve viable pregnancies, seem to be additionally dependent on the sperm origin. This was well shown by declining rates when spermatozoa in a relatively early stage of maturity had been used. We see increasing evidence that the degree of sperm maturity has an important impact on the outcome of ICSI. In obstructive azoospermia, spermatozoa retrieved from the epididymis should be used rather than testicular biopsy spermatozoa, or testicular sperm should be preincubated in culture medium before ICSI.     

特发性低促性腺激素型性腺功能减退患者KAL1基因突变分析

目的:分析男性特发性低促性腺激素型性腺功能减退(IHH)患者KAL1基因突变。方法:30例IHH患者运用聚合酶链反应-单链构象多态性(PCR-SSCP)结合PCR产物直接测序技术分析KAL1基因外显子突变。结果:在30例IHH患者中共发现3例KAL1基因突变,其中1例无义突变,为(c.1270C>T,p.R424X);2例移码突变,分别为(c.279_280delAG,p.G94fs)和(c.1886_1887delTT,p.L629fs)。结论:本文检测到3例KAL1基因突变,其中2例突变是新发现的突变,1例是文献报道过的突变,为IHH的分子遗传学研究积累了宝贵资料。