Assisted reproduction in male cancer survivors: fertility treatment and outcome in 67 couples

BACKGROUND: Many male cancer survivors experience fertility problems due to antineoplastic treatment. We report the fertility outcome in 67 couples referred to assisted reproduction treatment (ART) because of male factor infertility due to cancer. METHODS: This was a retrospective study assessing the following parameters: diagnosis, cancer treatment, type of fertility treatment and type of sperm used, number of pregnancies and pregnancy outcome. RESULTS: Testicular cancer and lymphomas were the most prevalent diagnoses. Adjuvant treatment with chemo- and/or radiation therapy had been given to 90% of the men. Semen was cryopreserved in 82% of the men prior to treatment. Following antineoplastic treatment, 43% of the men had motile spermatozoa in the ejaculate, but 57% were azoospermic. A total of 151 ART cycles were performed [55 intra-uterine insemination (IUI), 82 ICSI and 14 ICSI-frozen embryo replacement (FER)]. The clinical pregnancy rate per cycle was 14.8% after IUI, 38.6% after ICSI and 25% after ICSI-FER. The corresponding delivery rates were 11.1, 30.5 and 21%. Cryopreserved semen was used in 58% of the pregnancies. The delivery rate per cycle was similar after use of fresh or cryopreserved spermatozoa. CONCLUSIONS: Male cancer survivors have a good chance of fathering a child by using either fresh ejaculated sperm or cryopreserved sperm.     

Single nucleotide polymorphisms in the protamine-1 and -2 genes of fertile and infertile human male populations

Although various genetic factors have been implicated in human male infertility, the causative genes for the different types of idiopathic male infertility have not been elucidated. Protamines, which are the major DNA-binding proteins in the sperm nucleus, package the DNA into the sperm head. Analysis of the human protamine-1 (PRM1) and -2 (PRM2) gene sequences in 226 sterile male patients and in 270 proven-fertile male volunteers revealed four single nucleotide polymorphisms (SNPs) in the PRM1 coding region, which did not cause any amino acid substitutions, and one SNP in the PRM2 gene, which produced translation termination. We also observed one SNP in the 3' non-coding region of the PRM1 gene, and two SNPs within the intron of the PRM2 gene. The prevalence of these SNPs was similar in both infertile patients and in proven-fertile volunteers, except that the c248t alteration in the PRM2 gene induced a nonsense codon under conditions of heterozygosity in one infertile patient. Although the PRM1 and PRM2 genes are highly conserved, the single SNP in the PRM2 gene that induces translation termination may result in male infertility due to haploinsufficiency of PRM2.     

Effect of Dehydroepiandrosterone on Avoidance Behavior of Adult Male Rats

We studied the effect of repeated intraperitoneal treatment with dehydroepiandrosterone in doses of 0.1 and 0.7 mg/kg on conditioned-response activity and behavior of adult male rats. The effect of dehydroepiandrosterone on learning was estimated in conditioned active and passive avoidance response paradigms. Chronic administration of dehydroepiandrosterone in low and high doses had no effect on retention of conditioned passive avoidance response in adult male rats 24 h after learning. However, chronic administration of dehydroepiandrosterone in low dose impaired acquisition of the conditioned active avoidance response. It should be emphasized that chronic administration of dehydroepiandrosterone in high dose did not modulate acquisition and retention of this reaction.     

Recombinant follicle stimulating hormone: development of the first biotechnology product for the treatment of infertility. Recombinant Human FSH Product Development Group

Genes encoding the common gonadotrophin subunit and folliclestimulating hormone (FSH)-specific ß subunit wereisolated from a DNA library derived from human fetal liver cells,and inserted into separate expression vectors containing a selectable/amplifiablegene. These vectors were inserted into the genome of the Chinesehamster ovary cell line, resulting in expression of large amountsof biologically active human (h)FSH. This cell line was culturedon microcarrier beads in a large-scale bioreactor. hFSH in thecell culture supernatant was purified to homogeneity by a multistepprocess. The mature ß subunit had seven fewer aminoacid residues than reported in the literature and three otherdifferences were found in the sequence. Similar oligosaccharidestructures were present on recombinant (r)-hFSH and a purifiedurinary (u)-hFSH preparation. In-vitro and in-vivo, the biologicalactivities of u- and r-hFSH were indistinguishable, r-hFSH wasformulated in ampoules containing 75 IU FSH activity ( 7.5 µgFSH), which accounts for >99% of the protein content of thepreparation. Studies in non-human primates and human volunteersshowed the pharmacokinetics of u- and r-hFSH to be similar.In healthy volunteers, r-hFSH stimulated follicular developmentand induced significant increases in serum oestradiol and inhibin.Clinical experience with r-hFSH has shown it is more effectiveat stimulating ovarian follicle growth than urinary gonadotrophins.It is also effective at initiating spermatogenesis when giventogether with human chorionic gonadotrophin.     

Computer image sperm selection as a novel approach to subzonal insemination in the human

Utilizing real-time computer image analysis, individual spermatozoawere selected using microaspiration. Selection criteria werebased on potential hyperactivation motility characteristics;the amplitude of lateral head displacement >7.5 µm,curvilinear velocity >70 µm/s and linearity of <30%.For this pilot study, 16 patients (eight in each group) wererecruited. Using subzonal insemination (SUZI), up to five (mean= 4.4 ± 0.3) spermatozoa selected using computer-imagesperm selection (CISS) were microinjected, or up to 15 (mean= 12.8 ± 1.3 SD) unselected spermatozoa. In the groupwhich utilized CISS, 28 out of 49 (57%) oocytes were fertilizedcompared with 13 out of 52 (25%) utilizing conventional SUZI(P < 0.04); polyspermy was 20% (n = 10) and 2% (n = 1) respectively.CISS with SUZI showed increased efficiency in achieving fertilizationand is a novel approach to studying individual sperm functionin a sperm egg bioassay where gamete ratios are close to unity.     

The diagnosis of male infertility--prospective time-specific study of conception rates related to seminal analysis and post-coital sperm--mucus penetration and survival in otherwise unexplained infertility

Infertile women without any inherent female infertility factorsand able to secrete normal cervical mucus were studied prospectivelyin relation to post-coital sperm—mucus penetration (PCT)and their partner's seminal analysis, excluding men with azoospermia.Time-specific cumulative conception rates calculated as forlife-table analysis were related to each measured seminal variableon routine analysis of 2–3 samples (volume, density, proportionwith progressive motility, and proportion with normal morphology);to various derivatives from combinations of these variables;to seminal findings after vital staining; and to the PCT results.The best seminal predictor of fertility was the motile normalsperm density (MNSD), the 18 month conception rates being 57.4%+ 4.6 (SE) and 30.2% + 5.9 (ratio 1.9, P < 0.001) above andbelow a derived threshold value of 4 x 10⁶/ml. The PCT led torates of 55.6% ± 4.3 and 14.9% ± 5.1 (ratio 3.73,P < 0.001) for positive and negative results, respectively.The PCT also gave rise to a significantly distinct intermediatepoor-psitive sub-group (conception rate 30.6% ± 9.0).Seminal analysis (the MNSD) did not affect the conception rateassociated with a positive PCT but helped to discriminate furtherwith a negative PCT (conception rates 22.5% ± 8.7 withan MNSD above 4 x 10⁶/ml versus 5.6% ± 4.8 below, P <0.05). The PCT was the single best predictor of fertility butseminal analysis (the MNSD) was of additional value after anegative PCT.     

Changes in anti-Müllerian hormone serum concentrations over time suggest delayed ovarian ageing in normogonadotrophic anovulatory infertility

BACKGROUND: Anti-Müllerian hormone (AMH), produced by growing pre-antral and early antral ovarian follicles, has been shown to be a useful marker for ovarian ageing. Serum AMH concentrations are elevated during reproductive life in anovulatory women, especially in those patients exhibiting polycystic ovaries (PCO). The current study was designed to investigate whether the decrease in AMH serum concentrations over time is different comparing women with normogonadotrophic anovulation [World Health Organization (WHO) group 2 (including polycystic ovary syndrome (PCOS)] and normo-ovulatory controls. METHODS AND RESULTS: AMH serum levels were assessed on two occasions in 98 patients suffering from WHO 2 anovulatory infertility as well as in 41 normo-ovulatory premenopausal women. Median time interval between both visits was 2.6 years (range 0.3-9.0) for WHO 2 patients compared with 1.6 years (range 1.0-7.3) in controls. Serum AMH concentrations were significantly (P < 0.0001) elevated on both occasions in WHO 2 patients (AMH1, median = 7.5 microg/l, range 0.1-35.8; and AMH2, median = 6.7 microg/l, range 0.0-30.6) compared with controls (AMH1, median = 2.1 microg/l, range 0.1-7.4; and AMH2, median = 1.3 microg/l, range 0.0-5.0). Regression analysis, corrected for age, indicated a significant relative decrease in serum AMH concentrations over time for both groups (P < 0.001). However, the decline in serum AMH in WHO 2 patients was significantly less compared with controls (P = 0.03). CONCLUSION: The present longitudinal study shows that serum AMH concentrations decrease over time both in women presenting with WHO 2 anovulatory infertility and in normo-ovulatory controls. The decrease in WHO 2 patients is less pronounced despite distinctly elevated concentrations. This observation may suggest retarded ovarian ageing and hence a sustained reproductive life span in these patients.     

成年罪犯人格特征及父母教养方式的相关分析

目的：了解成年罪犯的人格特征及探讨父母教养方式与其人格的相关性。方法：对139名成年男性罪犯进行EPQ人格问卷,EMBU父母教养方式量表测试。结果：罪犯E、N、P分高于常模,L分低于常模,暴力型犯罪E分高于财产型犯罪。幼时家庭不完整者的“父母情感温暖、理解”、“父亲偏爱被试”因子分比幼时家庭完整者低。“父母情感温暖、理解”,“母亲过分干涉、过分保护”因子与E因子显著相关;“母子过分干涉、保护”及“母亲拒绝、否认”因子与N因子显著相关;“父母惩罚严厉、拒绝否认”因子与P因子显著相关。结论：罪犯的人格特征与父母教养方式显著相关。     

Testicular sperm extraction in azoospermic men submitted to bilateral orchidopexy

BACKGROUND: This study was carried out to evaluate whether bilateral orchidopexy represents a poor or good prognostic factor in azoospermic men undergoing testicular sperm extraction (TESE). METHODS: One hundred and seven presumed non-obstructive azoospermia (NOA) patients, according to conventional clinical parameters (volume of testis, FSH, clinical history) were submitted to testicular biopsy with TESE. Thirty men (28%) had a history of bilateral orchidopexy for cryptorchidism. RESULTS: Normal spermatogenesis or mild hypospermatogenesis was diagnosed in 12/30 ex-cryptorchid patients and in 7/77 presumed NOA patients (P = 0.0004). Conversely, pure Sertoli cell-only syndrome or complete maturation arrest was found in 10/30 ex-cryptorchid patients and in 48/77 presumed NOA patients (P = 0.0094). In 53/107 patients (49.5%), TESE allowed a positive sperm retrieval. At least one spermatozoon was observed in 22/30 ( approximately 73%) ex-cryptorchid patients and in 31/77 ( approximately 40%) presumed NOA patients (P = 0.0026). A large number of spermatozoa (equivalent to an obstructive pathology) were retrieved in 13/30 ex-cryptorchid and in 10/77 presumed NOA patients (P = 0.001). A history of bilateral orchidopexy in presumed NOA patients correlates positively for the chance of retrieving testicular spermatozoa (odds ratio 3.8; 95% confidence interval 1.41-10.21; P = 0.008). CONCLUSIONS: Although bilateral cryptorchidism is usually considered a testicular secretive dysfunction, TESE permits retrieval of a large number of spermatozoa in almost 40% of cases. Our data suggest the existence of congenital or acquired obstructive anomalies of the seminal ducts in azoospermic orchidopexed men.     

舟山海岛地区不育症患者的精液质量与年龄等因素的关系

目的探讨海岛不育男性精液质量与年龄、文化程度和不育时间的关系。方法采用统一调查表,对2004年3月~2005年9月在舟山市生殖研究中心门诊的228例不育症男性患者进行流行病学问卷调查及精液常规分析（SFA）。资料应用SPSS13.0统计软件进行处理。结果（1）研究对象的平均年龄为31.00岁,不育时间是3.00年;文化程度以初中为主,占24.12%,其次是高中,占20.18%;（2）b级、d级、正常形态和体部、尾部畸形精子比例在不同文化程度和年龄组之间的差异有统计学意义（P〈0.05）;（3）在不同的不育时间组之间极慢或不动（d级）精子比例有统计学意义（P〈0.05）。结论（1）生殖损害在年龄分布中有提前的趋势。（2）研究对象的年龄、文化程度和不育时间等因素可能与精液质量有关。