The prognostic role of the extent of Y microdeletion on spermatogenesis and maturity of Sertoli cells

Substantial involvement of the Y chromosome in sexual development and spermatogenesis has been demonstrated. Over the last decade, varying extent of Y chromosome microdeletions have been identified among infertile patients with azoospermia or oligozoospermia. These microdeletions were clustered in three main regions named AZFa, AZFb, and AZFc. Analysis of the Y chromosome microdeletion was found to be of prognostic value in cases of infertility, both in terms of clinical management as well as for understanding the aetiology of the spermatogenesis impairment. However, the accumulated data are difficult to analyse, due to the variable extent of these deletions, the different sequence-tagged sites (STS) used to detect the microdeletions, and the non-uniformity of the histological terminology used by different investigators. This debate discusses the chances of finding testicular spermatozoa in men with a varying extent of Y chromosome microdeletions. The genotype and germ cell findings in men with AZFa microdeletions as well as those that include more than a single AZF region are reviewed, as is the effect of Y chromosome AZF microdeletions on the maturity of the Sertoli cells.     

男性不育患者Y染色体微缺失的研究

目的研究无精子症和少精子症患者与Y染色体位点缺失的相关性，建立Y染色体微缺失的分子诊断方法。方法采用多重PCR技术对53例染色体核型正常的无精子症和少精子症患者以及5例正常男性的无精子因子（azoospermia factor，AZF）区域的6个STS位点进行检测。结果5例精液正常男性未检出Y染色体微缺失；53例患者中6例有AZF区域的微缺失，总缺失率为11．3％。结论Y染色体微缺失是严重生精障碍的重要原因之一，无精子因子（AZF）候选基因在精子发生过程中可能起重要作用。     

Developmental outcome at 2 years of age for children born after ICSI compared with children born after IVF

BACKGROUND: Since the introduction of ICSI in 1991, medical outcome studies on ICSI children have been performed, but few have addressed developmental outcome. Hence, this outcome was assessed by performing a standard developmental test on children born after ICSI as compared with children born after IVF, at the age of 2 years. METHODS: In a prospective study, the medical and developmental outcome of 439 children born after ICSI (378 singletons, 61 twins) were compared with those of 207 children born after IVF (138 singletons, 69 twins), at the age of 24-28 months. These children were part of a cohort of children followed since birth. Of children reaching the age of 24-28 months between May 1995 and March 2002, 44.3% (2375/5356) were examined by a paediatrician who was unaware of the type of treatment used for each couple. Of all the children born, 12.2% (439/3618) in the ICSI group and 11.9% (207/1738) in the IVF group underwent a formal developmental assessment using the Bayley Scale of Infant Development (mental scale) by a paediatrician blinded to the type of treatment. RESULTS: There was no significant difference in maternal educational level, maternal age, gestational age, parity, birthweight, neonatal complication rate or malformation rate at 2 years between ICSI and IVF singletons, or between ICSI and IVF twins. No significant difference was observed in the developmental outcome using the Bayley scale at the age of 24-28 months (raw scores or test age) between ICSI children or IVF children. A multivariate regression analysis for the singleton children indicated that parity, sex (boys had lower scores than girls) and age had a significant influence on the test result, but that the fertility procedure (ICSI versus IVF) did not influence the test result. ICSI children from fathers with low sperm concentration, low sperm motility or poor morphology had a similar developmental outcome to that of children from fathers with normal sperm parameters. There were no significant differences between the initial cohort and the group lost to follow-up, nor between the psychologically tested and the non-tested group for a number of variables such as maternal educational level, birthweight in singletons and neonatal malformation rate. Although only some of the cohort of ICSI children were evaluated, a representative sample of both ICSI and IVF children was compared. CONCLUSIONS: There is no indication that ICSI children have a lower psychomotor development than IVF children. Paternal risk factors associated with male-factor infertility were found not to play a role in developmental outcome.     

Genetic analysis of males from intracytoplasmic sperm injection couples

A total of 392 men referred for intracytoplasmic sperm injection (ICSI) participated in genetic analysis. The control group consisted of 100 normal fertile males. Chromosome and DNA analyses were performed to investigate the frequency of Y-chromosome microdeletions and CFTR mutations (the controls underwent DNA analysis only). An abnormal karyotype was found in 4.6% of all males, but the frequency among men with azoospermia was higher, at 11.7%. Y-chromosome microdeletions were found only among men with azoospermia (6.5%) and men with extreme oligospermia (2%). Compound heterozygosity for CFTR mutations was found in men with azoospermia (3.9%) and congenital bilateral absence of vas deferens (CBAVD) only. We conclude that all couples referred for ICSI should be offered chromosome analysis. DNA analysis for Y-chromosome microdeletions should be reserved for men with azoospermia or extreme oligospermia (<1 x 106 spermatozoa). Analysis for CFTR mutations should be limited to those with obstructive azoospermia or those with a family history of cystic fibrosis.     

Randomized comparison of ovulation induction with and without intrauterine insemination in the treatment of unexplained infertility

The aim of this prospective randomized controlled study wasto determine the possible role of ovulation induction with intrauterineinsemination (IUI) in the treatment of unexplained infertility.A total of 100 patients were randomized to receive ovulationinduction with or without IUI. All patients were treated withlong-course gonadotrophinreleasing hormone analogue (GnRHa),starting in the luteal phase, and exogenous follicle stimulatinghormone (FSH) to induce follicular growth. Ovulation was inducedusing human chorionic gonadotrophin and timed intercourse (TI)was advised 24–48 h later or IUI was effected 36—48h later. Both the cycle fecundities (21.8 and 8.5%) and thecumulative ongoing pregnancy rates after three cycles (42 and20%) were significantly higher (P < 0.03) in the IUI groupthan in the TI group respectively. This is a clear indicationthat ovulation induction with IUI is an effective treatmentmethod for unexplained infertility, but ovulation inductionwith TI has a negligible impact in this large group of patients.     

Intrauterine insemination treatment in subfertility: an analysis of factors affecting outcome

A total of 811 intrauterine insemination (IUI) cycles in which clomiphene citrate/human menopausal gonadotrophin (HMG) was used for ovarian stimulation were analysed retrospectively to identify prognostic factors regarding treatment outcome. The overall pregnancy rate was 12.6% per cycle, the multiple pregnancy rate 13.7%, and the miscarriage rate 23.5%. Logistic regression analysis revealed five predictive variables as regards pregnancy: number of the treatment cycle (P = 0.009), duration of infertility (P = 0.017), age (P = 0.028), number of follicles (P = 0.031) and infertility aetiology (P = 0.045). The odds ratios for age < 40 years, unexplained infertility aetiology (versus endometriosis) and duration of infertility < or = 6 years were 3.24, 2.79 and 2.33, respectively. A multifollicular ovarian response to clomiphene citrate/HMG resulted in better treatment success than a monofollicular response, and 97% of the pregnancies were obtained in the first four treatment cycles. The results indicate that clomiphene citrate/HMG/IUI is a useful and cost-effective treatment option in women < 40 years of age with infertility duration < or = 6 years, who do not suffer from endometriosis.     

Detection of structural and numerical chromosomal abnormalities by ACM-FISH analysis in sperm of oligozoospermic infertility patients

BACKGROUND: Modern reproductive technologies are enabling the treatment of infertile men with severe disturbances of spermatogenesis. The possibility of elevated frequencies of genetically and chromosomally defective sperm has become an issue of concern with the increased usage of ICSI, which can enable men with severely impaired sperm production to father children. Several papers have been published reporting aneuploidy in oligozoospermic patients, but relatively little is known about chromosome structural aberrations in the sperm of these patients. METHODS: We examined sperm from infertile, oligozoospermic individuals for structural and numerical chromosomal abnormalities using a multicolour ACM fluorescence in situ hybridization (FISH) assay that utilizes DNA probes specific for three regions of chromosome 1 to detect human sperm that carry numerical chromosomal abnormalities plus two categories of structural aberrations: duplications and deletions of 1pter and 1cen, and chromosomal breaks within the 1cen-1q12 region. RESULTS: There was a significant increase in the average frequencies of sperm with duplications and deletions in the infertility patients compared with the healthy concurrent controls. There was also a significantly elevated level of breaks within the 1cen-1q12 region. There was no evidence for an increase in chromosome 1 disomy, or in diploidy. CONCLUSIONS: Our data reveal that oligozoospermia is associated with chromosomal structural abnormalities, suggesting that oligozoospermic men carry a higher burden of transmissible, chromosome damage. The findings raise the possibility of elevated levels of transmissible chromosomal defects following ICSI treatment.     

Fibroids, infertility and pregnancy wastage

Uterine fibroids are often found in women of reproductive age. Different types of fibroids may affect reproductive outcome to a different extent, with submucous, intramural and subserosal fibroids being (in decreasing order of importance) a cause of infertility and pregnancy wastage. Fibroids may also produce a number of complications during pregnancy. Women who are scheduled for assisted conception should be advised to have submucous and possibly intramural fibroids removed prior to IVF. Large fibroids (>5 cm), wherever their location, should be considered individually, with the reproductive history being an important consideration. Miscarriage rates are significantly reduced following myomectomy. Open myomectomy should be the route of choice when there are large subserosal or intramural fibroids, multiple fibroids or entry into the uterine cavity is to be expected. Proper assessment of the benefits and risks of surgery for individual patients should be carefully considered before offering a procedure.     

子宫内膜异位症并不孕患者腹腔镜电灼术治疗前后外周血EmAb及CA125值的差异与分析

目的：考察腹腔镜电灼术治疗子宫内膜异位症的疗效以及子宫内胰异位症与 ＥｍＡｂ和 ＣＡ１２５的关系。方法：应用腹腔镜诊断、电灼治疗子宫内膜异位症患者８０例,测定手术前后患者外周血ＥｍＡｂ和ＣＡ１２５,考察术后复孕率,并与非ＥＭＴ组６０例及Ｄａｎａｚｏｌ治疗组１５０例进行比较。结果：①随着患者ＥＭＴ分期的升级,ＥｍＡｂ值也呈上升的趋势,两者间存在良好的线性相关关系（ｒ２＝０．８８６,Ｐ＜０．０１）．同样的趋势也出现在ＣＡ１２５中。②各期ＥＭＴ患者的术前 ＥｍＡｂ和 ＣＡ１２５ 值均较非 ＥＭＴ组高（Ｐ＜０．０１）。③在 Ｉ～Ⅲ期间,术后 ＥｍＡｂ与 ＣＡ１２５ 值均较术前有显著性下降（其中Ⅰ、Ⅲ期组Ｐ＜０．０１;Ⅲ期组Ｐ＜０．０５）。④就总体而言,Ⅰ～Ⅳ期ＥＭＴ患者之间外周血的 ＥｍＡｂ没有显著性差异（Ｐ＞０．０５）,相反,各组间的 ＣＡ１２５则存在非常显著性差异（Ｐ＜０．０１）。⑤各期患者的术前、后的ＥｍＡｂ与ＣＡ１２５值之间呈现出显著正相关关系（Ｐ＜０．０１）。⑥腹腔镜组患者复孕率为５１．２５％（４１／８０）,Ｄａｎａｚｏｌ组复孕率为５７．３３％（８６／１５０）,两组间无差异显著性（Ｐ＞０．０５）。结论：腹腔镜诊断和治     

子宫内膜异位症合并不孕者生殖内分泌的改变

[目的]通过检测血液及腹腔液中生殖内分泌激素水平,了解内分泌因素在子宫内膜异位症所致不孕中的作用.[方法]运用荧光微粒子发光法(MEIA),于卵泡期对78例不孕或子宫内膜异位症(EM)患者(EM合并不孕32例,单纯EM者20例,单纯不孕者26例)及14名健康绝育者的血液及腹腔液进行生殖内分泌激素的检测.[结果]EM者血中催乳素(PRL)、雌二醇(E2)及睾酮(T)水平高于无EM者(P<0.05),EM合并不孕者PRL及T高于EM非不孕者;重度EM的PRL、E2及T高于中度和轻度EM(P<0.05);无EM的不孕者除LH较正常对照组高外,其余与正常对照组之间无差异;卵泡刺激素(FSH)及孕酮(P)水平在以上各组之间无差异(P>0.05).EM合并不孕组腹腔液中PRL、LH、E2及T水平高于其他各组(P<0.05),而FSH及P与其他各组之间无差异(P>0.05).EM非不孕者PRL高于非EM不孕及正常对照组(P<0.05)、LH则与正常对照组无差异,但低于非EM不孕组(P<0.05),而FSH、E2及P与非EM不孕及正常对照组间无差异(P>0.05);非EM不孕组与正常对照组之间除LH较高外,其余各项无差异;不同程度EM组之间除FSH无差异外,其余各项均有差异,重度高于中度,中度又高于轻度EM(P<0.05).[结论]子宫内膜异位症特别是合并不孕者血及腹腔液中PRL和T水平较高,这可能是EM导致不孕的原因之一.